pituitrin and Hypertension

The automatism of cardiac pacemaker cells, which is tuned, is regulated by the autonomic nervous system (ANS) and multiple endocrine and paracrine factors, including cardiovascular peptides. The cardiovascular peptides (CPs) form a group of essential paracrine factors affecting the function of the heart and vessels. They may also be produced in other organs and penetrate to the heart via systemic circulation. The present review draws attention to the role of vasopressin (AVP) and some other cardiovascular peptides (angiotensins, oxytocin, cytokines) in the regulation of the cardiovascular system in health and cardiovascular diseases, especially in post-infarct heart failure, hypertension and cerebrovascular strokes. Vasopressin is synthesized mostly by the neuroendocrine cells of the hypothalamus. There is also evidence that it may be produced in the heart and lungs. The secretion of AVP and other CPs is markedly influenced by changes in blood volume and pressure, as well as by other disturbances, frequently occurring in cardiovascular diseases (hypoxia, pain, stress, inflammation). Myocardial infarction, hypertension and cardiovascular shock are associated with an increased secretion of AVP and altered responsiveness of the cardiovascular system to its action. The majority of experimental studies show that the administration of vasopressin during ventricular fibrillation and cardiac arrest improves resuscitation, however, the clinical studies do not present consisting results. Vasopressin cooperates with the autonomic nervous system (ANS), angiotensins, oxytocin and cytokines in the regulation of the cardiovascular system and its interaction with these regulators is altered during heart failure and hypertension. It is likely that the differences in interactions of AVP with ANS and other CPs have a significant impact on the responsiveness of the cardiovascular system to vasopressin in specific cardiovascular disorders.

Topics: Angiotensins; Arginine Vasopressin; Cardiovascular Diseases; Cardiovascular System; Cytokines; Heart Failure; Humans; Hypertension; Lung; Oxytocin; Vasopressins

The neurons secreting oxytocin (OXY) and vasopressin (AVP) are located mainly in the supraoptic, paraventricular, and suprachiasmatic nucleus of the brain. Oxytocinergic and vasopressinergic projections reach several regions of the brain and the spinal cord. Both peptides are released from axons, soma, and dendrites and modulate the excitability of other neuroregulatory pathways. The synthesis and action of OXY and AVP in the peripheral organs (eye, heart, gastrointestinal system) is being investigated. The secretion of OXY and AVP is influenced by changes in body fluid osmolality, blood volume, blood pressure, hypoxia, and stress. Vasopressin interacts with three subtypes of receptors: V1aR, V1bR, and V2R whereas oxytocin activates its own OXTR and V1aR receptors. AVP and OXY receptors are present in several regions of the brain (cortex, hypothalamus, pons, medulla, and cerebellum) and in the peripheral organs (heart, lungs, carotid bodies, kidneys, adrenal glands, pancreas, gastrointestinal tract, ovaries, uterus, thymus). Hypertension, myocardial infarction, and coexisting factors, such as pain and stress, have a significant impact on the secretion of oxytocin and vasopressin and on the expression of their receptors. The inappropriate regulation of oxytocin and vasopressin secretion during ischemia, hypoxia/hypercapnia, inflammation, pain, and stress may play a significant role in the pathogenesis of cardiovascular diseases.

Topics: Axons; Brain; Cardiovascular Abnormalities; Cardiovascular System; Humans; Hypertension; Lung; Myocardial Infarction; Neurons; Neurophysins; Oxytocin; Protein Precursors; Receptors, Oxytocin; Vasopressins

Angiotensin II (ANG II) and vasopressin (VP) interact in several physiological mechanisms, playing a role in arterial hypertension and congestive heart failure. Aim and Methods of Search: To overview the primary mechanism involved in the regulation of cardiovascular function, PubMed/Medline was searched, and authors selected original articles and reviews written in English.. Angiotensin II (ANG II) and vasopressin (VP) are involved in several physiological mechanisms. ANG II stimulates VP release via angiotensin receptor 1. ANG II and VP stimulate aldosterone synthesis and secretion and enhance its action at the renal collecting duct level. VP is also involved in the cardiovascular reflex control of the sympathetic nervous system (SNS). Also, VP potentiates vasoconstriction and cardiac contractility, enhancing the effect of ANG II on sympathetic tone and arterial pressure. On the other hand, ANG II and VP act antagonistically in regulating baroreflex control of the SNS. There is evidence that high VP plasma levels increase baroreflex sympatho-inhibitory responses, and the arterial baroreflex response is shifted to lower pressure. This cardiovascular reflex control is mediated mainly in the brain, specifically in the circumventricular organ area postrema (AP). The modulation of cardiovascular reflex control induced by VP is abolished after lesions of the AP. VP modulation of baroreflex function is also under the control of α2-adrenergic pathway arising from the nucleus of the solitary tract (NTS) and synapsing on VP-ergic neurons of supraoptic and paraventricular nuclei. Presynaptic α2-adrenergic stimulation within the NTS inhibits VP release induced by hypovolemia and the effects of VP and AP on baroreflex control of SNS, thus showing baroreceptor afferent inputs are processed within the NTS and contribute to the increased baroreflex sympatho-inhibitory responses.. In patients with congestive heart failure (CHF), plasma VP levels are elevated, inducing an up-regulation of aquaporin 2 water channel expression in renal collecting duct (CD) cells provoking exaggerated water retention and dilutional hyponatremia. Antagonists of VP and ANG II receptors reduce edema, body weight, and dyspnea in CHF patients.. Hormonal imbalance between ANG II, VP, and SNS may induce hypertension and impaired water-electrolyte balance in cardiovascular diseases.

Topics: Angiotensin II; Animals; Cardiovascular Physiological Phenomena; Cardiovascular System; Heart Failure; Humans; Hypertension; Receptor Cross-Talk; Reflex, Abnormal; Sympathetic Nervous System; Vasopressins

It has been postulated that intraocular pressure, an important glaucoma risk factor, correlates positively with arterial blood pressure (blood pressure). However, results of experimental and clinical studies are often contradictory. It is hypothesized that, in some hypertensive patients, disturbances in intraocular pressure regulation may depend on biological effects of blood borne hormones underlying a particular type of hypertension, rather than on blood pressure level itself.. This review compares the effects of hormones on blood pressure and intraocular pressure, in order to identify a hormonal profile of hypertensive patients with an increased risk of intraocular pressure surge. The PUBMED database was searched to identify pre-clinical and clinical studies investigating the role of angiotensin II, vasopressin, adrenaline, noradrenaline, prostaglandins, and gaseous transmitters in the regulation of blood pressure and intraocular pressure.. Studies included in the review suggest that intraocular and blood pressures often follow a different pattern of response to the same hormone. For example, vasopressin increases blood pressure, but decreases intraocular pressure. In contrast, high level of nitric oxide decreases blood pressure, but increases intraocular pressure.. Arterial hypertension is associated with altered levels of blood borne hormones. Contradicting results of studies on the relationship between arterial hypertension and intraocular pressure might be partially explained by diverse effects of hormones on arterial and intraocular pressures. Further studies are needed to evaluate if hormonal profiling may help to identify glaucoma-prone patients.

Topics: Blood Pressure; Glaucoma; Humans; Hypertension; Intraocular Pressure; Neurophysins; Protein Precursors; Vasopressins

We present recent advances in understanding of the role of vasopressin as a neurotransmitter in autonomic nervous system control of the circulation, emphasizing hypothalamic mechanisms in the paraventricular nucleus (PVN) involved in controlling sympathetic outflow toward the cardiovascular system.. Suggest that somato-dendritically released vasopressin modulates the activity of magnocellular neurons in the PVN and SON, their discharge pattern and systemic release. Advances have been made in uncovering autocrine and paracrine mechanisms controlling presympathetic neuron activity, involving intranuclear receptors, co-released neuroactive substances and glia. It is now obvious that intranuclear release of vasopressin and the co-release of neuroactive substances in the PVN, as well as the level of expression of vasopressin receptors, modulate sympathetic outflow to the cardiovascular system and determine vulnerability to stress. Further research involving patho-physiological models is needed to validate these targets and foster the development of more efficient treatment.

Topics: Animals; Autonomic Nervous System; Blood Pressure; Cardiovascular System; Humans; Hypertension; Neurons; Neurophysins; Paraventricular Hypothalamic Nucleus; Protein Precursors; Receptors, Vasopressin; Vasopressins

The objective of this review is to provide an in-depth evaluation of how renal nerves regulate renal and cardiovascular function with a focus on long-term control of arterial pressure. We begin by reviewing the anatomy of renal nerves and then briefly discuss how the activity of renal nerves affects renal function. Current methods for measurement and quantification of efferent renal-nerve activity (ERNA) in animals and humans are discussed. Acute regulation of ERNA by classical neural reflexes as well and hormonal inputs to the brain is reviewed. The role of renal nerves in long-term control of arterial pressure in normotensive and hypertensive animals (and humans) is then reviewed with a focus on studies utilizing continuous long-term monitoring of arterial pressure. This includes a review of the effect of renal-nerve ablation on long-term control of arterial pressure in experimental animals as well as humans with drug-resistant hypertension. The extent to which changes in arterial pressure are due to ablation of renal afferent or efferent nerves are reviewed. We conclude by discussing the importance of renal nerves, relative to sympathetic activity to other vascular beds, in long-term control of arterial pressure and hypertension and propose directions for future research in this field. © 2017 American Physiological Society. Compr Physiol 7:263-320, 2017.

Topics: Animals; Arterial Pressure; Humans; Hypertension; Kidney; Models, Animal; Neurons, Afferent; Neurons, Efferent; Osmoregulation; Sympathetic Nervous System; Vascular Resistance; Vasopressins

Dietary salt intake increases both plasma sodium and osmolality and therefore increases vasopressin (VP) release from the neurohypophysis. Although this effect could increase blood pressure by inducing fluid reabsorption and vasoconstriction, acute activation of arterial baroreceptors inhibits VP neurons via GABA. Two recent studies showed that chronic high sodium intake causes an increase in intracellular chloride concentration in VP neurons. This effect causes GABA

Topics: Animals; Blood Pressure; Humans; Hypertension; Male; Osmolar Concentration; Pressoreceptors; Rats; Sodium Chloride; Sodium Chloride, Dietary; Vasopressins

The pathologic consequences of sodium retention in the CKD population can lead to hypertension, edema, and progressive disease. Sodium excess is responsible for increases in oxidative stress, which alters kidney vasculature. As progression of CKD occurs, hyperfiltration by remaining nephrons compensates for an overall decrease in the filtered load of sodium. In the later stages of CKD, compensatory mechanisms are overcome and volume overload ensues. Nephrotic syndrome as it relates to sodium handling involves a different pathophysiology despite a common phenotype. Extrarenal sodium buffering is also examined as it has significant implications in the setting of advanced CKD.

Topics: Animals; Atrial Natriuretic Factor; Diet, Sodium-Restricted; Homeostasis; Humans; Hypertension; Nephrotic Syndrome; Oxidative Stress; Renal Insufficiency, Chronic; Renin-Angiotensin System; Skin; Sodium; Sympathetic Nervous System; Vasopressins

Chronic kidney disease (CKD) imposes a significant global health burden. In the United States, one in three adults are at risk for CKD currently affecting over 28 million Americans. While several studies have demonstrated the benefit of treating traditional risk factors in CKD, including hypertension with pharmacologic agents such as blockade of the renin-angiotensin system (RAAS), there is scarce data on the advantages of sodium and fluid management in this population. Both experimental and observational studies have shown improvement in hypertension and cardiovascular outcomes with sodium restriction to ≤2.3 grams per day, however, to date there are very few randomized controlled trials demonstrating a benefit in sodium reduction for the prevention or progression of CKD. Similarly, studies on increasing fluid consumption have shown to be advantageous in polycystic kidney disease as well as chronic nephrolithiasis, yet no randomized controlled trials exist on the fluid management in patients with kidney disease. This review aims to explore the evidence of sodium restriction and fluid management in the CKD population as well as underlying mechanisms and clinical barriers of sodium and water management as conservative therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Diseases; Conservative Treatment; Disease Progression; Fluid Therapy; Humans; Hypertension; Hypertrophy, Left Ventricular; Hyponatremia; Polycystic Kidney Diseases; Renal Insufficiency, Chronic; Renin-Angiotensin System; Risk Factors; Sodium Chloride; United States; Vasopressins

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic renal disease in adults, affecting one in every 1000 Australians. It is caused by loss-of-function heterozygous mutations in either PKD1 or PKD2 , which encode the proteins, polycystin-1 and polycystin-2 respectively. The disease hallmark is the development of hundreds of microscopic fluid-filled cysts in the kidney during early childhood, which grow exponentially and continuously through life at varying rates (between 2% and 10% per year), causing loss of normal renal tissue and up to a 50% lifetime risk of dialysis-dependent kidney failure. Other systemic complications include hypertensive cardiac disease, hepatic cysts, intracranial aneurysms, diverticular disease and hernias. Over the last two decades, advances in the genetics and pathogenesis of this disease have led to novel treatments that reduce the rate of renal cyst growth and may potentially delay the onset of kidney failure. New evidence indicates that conventional therapies (such as angiotensin inhibitors and statins) have mild attenuating effects on renal cyst growth and that systemic levels of vasopressin are critical for promoting renal cyst growth in the postnatal period. Identifying and integrating patient-centred perspectives in clinical trials is also being advocated. This review will provide an update on recent advances in the clinical management of ADPKD.

Topics: Angiotensin Receptor Antagonists; Disease Management; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Mutation; Polycystic Kidney, Autosomal Dominant; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency; TRPP Cation Channels; Vasopressins

This review assessed the utility of vasopressin and vasopressin analogues for the treatment of refractory hypotension associated with angiotensin-converting enzyme (ACE) inhibitors in the perioperative setting. A systematic review of the literature was conducted using MEDLINE, Embase, and ProQuest. Six randomized controlled trials met eligibility criteria. In the perioperative setting, continued use of ACE inhibitors within 24 hours before surgery remains controversial. Authors of the reviewed studies suggested that the morning dose of the ACE inhibitor be held, and those patients experienced decreased catecholamine use postoperatively and shorter duration of decreased mean arterial pressure. No incidence of refractory hypertension from withholding the morning dose of the ACE inhibitor was mentioned. All of the patients receiving vasopressin demonstrated improved hemodynamic stability with small, intermittent doses, without profound ischemic changes. For management (prevention and treatment) of ACE inhibitor-associated hypotension in the perioperative setting, all studies showed statistically significant success with vasopressin or vasopressin analogues for improvement of systemic blood pressures. Before vasopressin is widely accepted as a standard of care, further studies are needed to confirm these findings and assess the general utility of vasopressin in surgical populations for management of ACE inhibitor-associated refractory hypotension.

Topics: Anesthesia, General; Angiotensin-Converting Enzyme Inhibitors; Humans; Hypertension; Hypotension; Vasopressins

The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the central nervous system. Increased activation of the central nervous system, driving enhanced sympathetic outflow and increased blood pressure, has emerged as a major contributor to the pathogenesis of hypertension. The hypothalamus is a key brain site acting to integrate central and peripheral inputs to ultimately impact blood pressure in multiple disease states that evoke hypertension. This review highlights recent advances that have identified novel signal transduction mechanisms within multiple hypothalamic nuclei (e.g., paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of hypertension in neurogenic hypertension, angiotensin II hypertension, salt-sensitive hypertension, chronic intermittent hypoxia, and obesity-induced hypertension. Increased understanding of hypothalamic activity in hypertension has the potential to identify novel targets for future therapeutic interventions designed to treat hypertension.

Topics: Animals; Humans; Hypertension; Hypothalamus; Inflammation; Oxidative Stress; Signal Transduction; Vasopressins

Autosomal dominant polycystic kidney disease (ADPKD), which frequently leads to end-stage renal disease, currently has no specific drug therapies. Better understanding of its pathogenesis and recent clinical trials have led to more accurate diagnosis of the disease and its manifestations, as well as to promising new approaches to treatment.

Topics: Drug Discovery; Humans; Hypertension; Intracranial Aneurysm; Pain; Polycystic Kidney, Autosomal Dominant; Signal Transduction; TOR Serine-Threonine Kinases; Urinary Tract Infections; Vasopressins

Autosomal dominant polycystic kidney disease (ADPKD) is the world's most common inherited kidney disease. An increasing number of animal and human studies have enhanced our understanding of the molecular and cellular pathology of ADPKD. New treatment options are being tested in clinical trials in spite of the failure of mammalian target of rapamycin inhibitor therapy. The main and most effective therapy remains control of hypertension by renin-angiotensin-aldosterone system (RAAS) blockade. This review focuses only on promising therapies, including dual inhibition of RAAS, vasopressin receptor antagonists, increased fluid intake, and blockade of certain receptors of cyclic adenosine monophosphate. Also, the paper reviews what these advances mean to patients and clinicians and elaborates on how these changes can be immediately applied to clinical practice. There is an urgent need for discovery of new therapies targeted toward ADPKD in comparison with therapeutic progress of all other renal diseases.

Topics: AMP-Activated Protein Kinases; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Disease Progression; Enzyme Activators; Fluid Therapy; Hormone Antagonists; Humans; Hypertension; Polycystic Kidney, Autosomal Dominant; Renin-Angiotensin System; Risk Reduction Behavior; Treatment Outcome; Vasopressins

The association between fructose and increased blood pressure is still incompletely defined, because experimental studies have produced dissimilar conclusions. Amplified vasopressor responses to minimal stimuli and differing responses to fructose in peripheral versus central sites may explain the controversy. Fructose induces systemic hypertension through several mechanisms mainly associated with deleterious effects on target organs (kidney, endothelium, heart) exerted by the byproducts of its metabolism, such as uric acid. The kidney is particularly sensitive to the effects of fructose because high loads of this sugar reach renal tissue. In addition, fructose increases reabsorption of salt and water in the small intestine and kidney; thus the combination of salt and fructose has a synergistic effect in the development of hypertension. Clinical and epidemiologic studies have also linked fructose consumption with hypertension. Further studies are warranted in order to understand the role of fructose in the development of hypertension.

Topics: Animals; Blood Pressure; Disease Models, Animal; Endothelium, Vascular; Fructose; Humans; Hypertension; Kidney Diseases; Metabolic Syndrome; Oxidative Stress; Risk Factors; Sodium Chloride, Dietary; Sweetening Agents; United States; Uric Acid; Vasopressins

Excessive sodium reabsorption by the kidney has long been known to participate in the pathogenesis of some forms of hypertension. In the kidney, the final control of NaCl reabsorption takes place in the distal nephron through the amiloride-sensitive epithelial sodium channel (ENaC). Liddle's syndrome, an inherited form of hypertension due to gain-of-function mutations in the genes coding for ENaC subunits, has demonstrated the key role of this channel in the sodium balance. Although aldosterone is classically thought to be the main hormone regulating ENaC activity, several studies in animal models and in humans highlight the important effect of vasopressin on ENaC regulation and sodium transport. This review summarizes the effect of vasopressin V2 receptor stimulation on ENaC activity and sodium excretion in vivo. Moreover, we report the experimental and clinical data demonstrating the role of renal ENaC in water conservation at the expense of a reduced ability to excrete sodium. Acute administration of the selective V2 receptor agonist dDAVP not only increases urine osmolality and reduces urine flow rate but also reduces sodium excretion in rats and humans. Chronic V2 receptor stimulation increases blood pressure in rats, and a significant correlation was found between blood pressure and urine concentration in healthy humans. This led us to discuss how excessive vasopressin-dependent ENaC stimulation could be a risk factor for sodium retention and resulting increase in blood pressure.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Epithelial Sodium Channels; Humans; Hypertension; Kidney; Rats; Receptors, Vasopressin; Risk Factors; Sodium; Vasopressins; Water

Topics: Acute Disease; Anti-Anxiety Agents; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Cardiac Pacing, Artificial; Dopamine; Drug Overdose; Fluid Therapy; Humans; Hypertension; Hypotension; Isoproterenol; Nitroglycerin; Poisoning; Practice Guidelines as Topic; Propranolol; Vasopressins

Topics: Cushing Syndrome; Edema; Humans; Hyperaldosteronism; Hypertension; Hypokalemia; Hyponatremia; Inappropriate ADH Syndrome; Mineralocorticoid Excess Syndrome, Apparent; Renin-Angiotensin System; Vasopressins

Topics: Body Water; Diabetes Insipidus; Electrolytes; Humans; Hyperaldosteronism; Hypertension; Hypoaldosteronism; Inappropriate ADH Syndrome; Natriuretic Peptides; Renin-Angiotensin System; Vasopressins; Water-Electrolyte Imbalance

Vasopressin, synthesized in the hypothalamus, is released by increased plasma osmolality, decreased arterial pressure, and reductions in cardiac volume. Three subtypes of vasopressin receptors, V1, V2, and V3, have been identified, mediating vasoconstriction, water reabsorption, and central nervous system effects, respectively. Vasopressin and its analogs have been studied intensively for the treatment of states of "relative vasopressin deficiency," such as sepsis, vasodilatory shock, intraoperative hypotension, and cardiopulmonary resuscitation. Infusion of vasopressin (0.01-0.04 U/min) decreases catecholamine requirements in patients with sepsis and other types of vasodilatory shock. Bolus application of 1 mg terlipressin, the V1 agonist, reverses refractory hypotension in anesthetized patients and has been studied in patients with septic shock and chronic liver failure. During cardiopulmonary resuscitation, a 40-U bolus dose of vasopressin may be considered to replace the first or second bolus of epinephrine regardless of the initial rhythm. The side effects of vasopressin and its analogs must be further characterized.

Topics: Adrenocorticotropic Hormone; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Cardiopulmonary Resuscitation; Hemostasis; Humans; Hypertension; Hypertension, Portal; Neuroendocrine Tumors; Shock, Septic; Vasopressins; Water-Electrolyte Balance

Growing number of studies reveal that the brain neural network plays significant role in the short-term and long-term regulation of the cardiovascular functions. The neurons involved in the complex neurogenic control of the cardiovascular system use classical neurotransmitters and nonconventional mediators such as peptides (angiotensin II, vasopressin, natriuretic peptides, endothelins, opioids, cytokines), steroids, ouabain-like factors and gaseous compounds. Among them the neuropeptides form a group of substances arising significant interest. Thanks to wide distribution of peptidergic neurons in the central nervous system, location of peptide receptors on neurons and glial cells, versatile but frequently overlapping mechanisms of activation of the intracellular processes the neuropeptides play significant role in short-term and long-term regulation of excitability and remodeling of the neurons. In several instances they modulate effects of the classical transmitting systems involved in regulation blood pressure, heart rate, water-electrolyte balance, metabolism, stress, pain, mood and memory. Prolonged activation or inhibition of specific neuropeptide pathways frequently results in long-lasting disorders of several regulatory systems. In this review this is exemplified by overactivity of angiotensin II, vasopressin and cytokines in the brain during hypertension, heart failure and stress. Multifarious actions of angiotensin II and vasopressin, and their mutual interaction with cytokines make of these neuropeptides excellent candidates for the compounds responsible for long-term resetting of the central cardiovascular control, and forming a link between the cardiovascular diseases, stress and mood disorders.

Topics: Angiotensin II; Brain; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cytokines; Heart Failure; Humans; Hypertension; Nerve Net; Neuropeptides; Neurosecretory Systems; Stress, Psychological; Vasopressins

Topics: Animals; Humans; Hypertension; Vasopressins

Blood pressure is maintained for preventing from the progression of damage of central nervous system. Endocrine system plays important roles in the prevention from the damage through the functional deviation. Hypertension is one of the results of the endocrinological deviation. Although the hypertension induced by the endocrinological deviation is a risk for the progression of metabolic syndrome, it is important in the maintaining activity of central nervous system.

Topics: Aged; Aging; Arteriosclerosis; Atrial Natriuretic Factor; Blood Volume; Cardiac Output; Central Nervous System; Endocrine System; Glucocorticoids; Growth Substances; Humans; Hypertension; Metabolic Syndrome; Parathyroid Hormone; PPAR gamma; Renin-Angiotensin System; Risk; Vascular Resistance; Vasopressins

In the kidney, the fine control of NaCl absorption takes place in the distal nephron and is controlled by aldosterone and vasopressin. This review summarizes the effects of vasopressin on Na+ transport mediated by the amiloride-sensitive epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel in immortalized or primary cultured cortical collecting duct cells, expressing either the wild-type ENaC subunits, or mutations, or deletions of the PY domain of the beta- or gamma-ENaC subunits responsible for Liddle's syndrome, an inherited form of hypertension due to excessive salt absorption.

Topics: Absorption; Aldosterone; Amiloride; Animals; Cells, Cultured; Chlorides; Cystic Fibrosis Transmembrane Conductance Regulator; Deamino Arginine Vasopressin; Epithelial Sodium Channels; Humans; Hypertension; Ion Transport; Kidney Tubules, Collecting; Mice; Mice, Mutant Strains; Models, Biological; Natriuresis; Oocytes; Protein Subunits; Recombinant Fusion Proteins; Sodium Channels; Sodium Chloride; Syndrome; Vasopressins; Water-Electrolyte Balance; Xenopus laevis

Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome, and excess risk remains even in effectively treated patients. The cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia. This review analyses the relationship of cortisol excess, both locally and at tissue level, to these cardiovascular risk factors, and to putative mechanisms for hypertension. Previous studies have examined correlations between cortisol, blood pressure, and other parameters in the general population and in Cushing's syndrome. This review also details changes induced by short-term cortisol administration in normotensive healthy men.

Topics: Blood Pressure; Cardiac Output; Cardiovascular Diseases; Cushing Syndrome; Female; Humans; Hydrocortisone; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin Resistance; Male; Obesity; Plasma Volume; Renin-Angiotensin System; Risk Factors; Sympathetic Nervous System; Vascular Resistance; Vasodilation; Vasopressins

Topics: Angiotensin-Converting Enzyme Inhibitors; Arginine; Chronic Disease; Diagnosis, Differential; Diuretics; Drug Therapy, Combination; Endothelin-1; Heart Failure; Humans; Hypertension; Prognosis; Renin-Angiotensin System; Vasopressins

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Cardiomegaly; Catecholamines; Humans; Hypertension; Hyperthyroidism; Hypothyroidism; Myocardial Contraction; Receptors, Thyroid Hormone; Renin-Angiotensin System; Thyroxine; Triiodothyronine; Vascular Resistance; Vasopressins

In this review, we will focus on the central neural mechanisms that couple osmotic perturbations to changes in sympathetic nerve discharge, and the possible impact these actions have in cardiovascular diseases such as arterial hypertension and congestive heart failure.. Changes in extracellular fluid osmolality lead to specific regulatory responses in defence of body fluid and cardiovascular homeostasis. Systemic hyperosmolality is well known to stimulate thirst and the release of antidiuretic hormone. These responses are largely due to osmosensing neurones in the forebrain lamina terminalis and hypothalamus and are critical elements in a control system that operates to restore body fluid osmolality. An equally important, but less characterized, target of central osmoregulatory processes is the sympathetic nervous system.. Understanding the neurobiology of sympathetic responses to changes in osmolality has important implications for body fluid and cardiovascular physiology. By stabilizing osmolality, vascular volume is preserved and thereby relatively normal levels of cardiac output and arterial pressure are maintained.

Topics: Animals; Blood Pressure; Dogs; Extracellular Space; Heart Failure; Humans; Hypertension; Intracellular Fluid; Kidney; Osmolar Concentration; Prosencephalon; Rats; Sodium Chloride; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Balance

Topics: Amino Acid Sequence; Animals; Calcium Signaling; Cardiac Output, Low; Cytokines; Endothelins; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Molecular Sequence Data; Natriuretic Peptide, Brain; Peptide Hydrolases; Renin-Angiotensin System; Sodium-Hydrogen Exchangers; Vasopressins

The biological clock, the suprachiasmatic nucleus (SCN), is essential for our daily well-being. It prepares us for the upcoming period of activity by an anticipatory rise in heart rate, glucose and cortisol. At the same time the 'hormone of the darkness', melatonin, decreases. Thus, the time-of-day message penetrates into all tissues, interestingly not only by means of hormones but also by a direct neuronal influence of the SCN on the organs of the body. The axis between the SCN and the paraventricular nucleus of the hypothalamus (PVN) is crucial for the organization/synchronization of the neuroendocrine and autonomic nervous system with the time of day. This SCN-neuroendocrine PVN axis takes care of a timely hormonal secretion. At the same time, the SCN-autonomic PVN axis fine-tunes the organs by means of the autonomic nervous system for the reception of these hormones. Finally, the similar organization of the projections of the human SCN as compared with that in the rodent brain suggests that these basic principles of neuroendocrine autonomic interaction may also be true in the human. The physiological data collected in humans thus far seem to support this hypothesis, while pathological changes in the SCN of humans suffering from depression or hypertension indicate a role for the SCN in the etiology of these diseases.

Topics: Animals; Autonomic Nervous System; Behavior; Biological Clocks; Circadian Rhythm; Depression; gamma-Aminobutyric Acid; Humans; Hypertension; Mammals; Pituitary Hormones; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

Dopamine, a neurotransmitter, precursor of noradrenaline, is responsible for cardiovascular and renal actions, such as increase in myocardial contractility and cardiac output, without changes in heart rate, producing passive and active vasodilatation, diuresis and natriuresis. These cardiovascular and renal actions take place through the interaction with dopamine receptors, D(1), D(2), D(3), D(4), and D(5). Recent findings point to the possibility of D(6) and D(7)receptors. Dopamine is known to influence the control of arterial pressure by influencing the central and peripheral nervous system and target organs such as kidneys and adrenal glands, in some types of hypertension. Although dopamine and its derivatives have been shown to have antihypertensive effects, these are still being studied; therefore it is important to explain some physiological and pharmacological aspects of dopamine, its receptors, and the clinical uses it could have in the treatment of arterial hypertension and more recently in obesity, based on evidence proving a clear association between obesity and the decrease in the expression of D(2) receptors in the brain of obese persons.

Topics: Angiotensin II; Animals; Dopamine; Dopamine Agonists; Humans; Hypertension; Nitric Oxide; Obesity; Protein Kinase C; Rats; Receptors, Dopamine; Risk Factors; Sodium-Hydrogen Exchangers; Vasopressins

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. Alterations in the following substances are discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, and corticotropin-releasing factor. Functional changes in these substances occur throughout the hypothalamus but are particularly prominent rostrally; most lead to an increase in sympathetic nervous activity which is responsible for the rise in arterial pressure. A few appear to be depressor compensatory changes. The majority of the hypothalamic changes begin as the pressure rises and are particularly prominent in the young rat; subsequently they tend to fluctuate and overall to diminish with age. It is proposed that, with the possible exception of the Dahl salt-sensitive rat, the hypothalamic changes associated with hypertension are caused by renal and intrathoracic cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a result of renal ischemia and trauma as in the reduced renal mass rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it is submitted, is due to the associated documented impaired ability to excrete sodium. It is proposed, therefore, that the hypothalamic changes in hypertension are a link in an integrated compensatory natriuretic response to the kidney's impaired ability to excrete sodium.

Topics: Acetylcholine; Angiotensins; Animals; Blood Pressure; Brain; Catecholamines; Enzyme Inhibitors; gamma-Aminobutyric Acid; Hemostatics; Histamine; Humans; Hypertension; Hypothalamus; Kidney; Neurons; Nitric Oxide; Ouabain; Peptides; Serotonin; Thyrotropin-Releasing Hormone; Vasopressins

Overactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several experimental animal models. We have recently reported that, in the murine brain RAS, angiotensin II (AngII) is converted by aminopeptidase A (APA) into angiotensin III (AngIII),which is itself degraded by aminopeptidase N (APN), both peptides being equipotent to increase vasopressin release and arterial blood pressure when injected by the intracerebroventricular (i.c.v.) route. Because AngII is converted in vivo into AngIII, the exact nature of the active peptide is not precisely known. To delineate their respective roles in the central control of cardiovascular functions, specific and selective APA and APN inhibitors are needed to block the metabolic pathways of AngII and AngIII respectively. In the absence of such compounds for APA, we first explored the organization of the APA active site by site-directed mutagenesis. This led us to propose a molecular mechanism of action for APA similar to that proposed for the bacterial enzyme thermolysin deduced from X-ray diffraction studies. Secondly, we developed a specific and selective APA inhibitor, compound EC33 [(S)-3-amino-4-mercaptobutylsulphonic acid], as well as a potent and selective APN inhibitor, PC18 (2-amino-4-methylsulphonylbutane thiol). With these new tools we examined the respective roles of AngII and AngIII in the central control of arterial blood pressure. A central blockade of APA with the APA inhibitor EC33 suppressed the pressor effect of exogenous AngII, suggesting that brain AngII must be converted into AngIII to increase arterial blood pressure. Furthermore, EC33, injected alone i.c.v. but not intravenously, caused a dose-dependent decrease in arterial blood pressure by blocking the formation of brain AngIII but not systemic AngIII. This is corroborated by the fact that the selective APN inhibitor PC18 administered alone via the i.c.v. route increased arterial blood pressure. This pressor response was blocked by prior treatment with the angiotensin type 1 receptor antagonist losartan, showing that blocking the action of APN on AngIII metabolism leads to an increase in endogenous AngIII levels, resulting in arterial blood pressure increase through an interaction with angiotensin type 1 receptors. These results demonstrate that AngIII is a major effector peptide of the brain RAS, exerting a tonic stimulatory control over arterial blood pressure. Thus AP

Topics: Aminopeptidases; Angiotensin II; Angiotensin III; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Arteries; Binding Sites; Blood Pressure; Brain; CD13 Antigens; Dose-Response Relationship, Drug; Glutamyl Aminopeptidase; Hypertension; Hypothalamus; Losartan; Mice; Models, Chemical; Mutagenesis, Site-Directed; Peptides; Rats; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Renin-Angiotensin System; Thermolysin; Vasopressins

Outcomes of recently published studies showed that cause of primary hypertension may lay in dysregulation of one of physiological mechanisms. Accordingly to current knowledge one can state that disturbance of every of these mechanisms results in cascade of changes in function of sympathetic and endocrine systems with special impact in renin-angiotensin-aldosterone system. Better understanding of mechanisms underlying the pathogenesis of primary hypertension is crucial in development of such a treatment that not only reduces blood pressure but also prevents cardiovascular complications of hypertension.

Topics: Aldosterone; Angiotensin II; Endothelins; Humans; Hypertension; Neuropeptide Y; Nitric Oxide; Renin; Vasopressins

1. A hormonal-sympathetic reflex model for long-term control of arterial pressure is presented. It is hypothesized that the hormonal-sympathetic reflex regulates arterial pressure during chronic dietary salt loading by decreasing sympathetic tone. This sympathetic response is mediated by an increase in plasma vasopressin (AVP) and a decrease in plasma angiotensin (AngII). 2. Three new models of neurogenic salt-dependent hypertension are presented. All models are theoretically based on an impaired hormonal-sympathetic reflex. 3. In the first model, sympathetic responsiveness is 'clamped' by long-term alpha-adrenergic blockade with prazosin. Prazosin treated rats exhibit marked salt-dependent hypertension despite normal suppression of the renin-angiotensin system. 4. In the second model, the ability of the central nervous system to respond to salt-induced changes in AVP and AngII concentrations was prevented by long-term administration of antagonists selective for the AVP-V1 and AT1. This 'clamp' of the afferent hormonal signal resulted in salt-dependent hypertension identical in magnitude to that observed in prazosin treated rats. 5. In the third model, the long-term arterial pressure responses to increasing dietary salt were examined in sino-aortic denervated (SAD) rats. SAD rats exhibited salt-dependent hypertension, of lesser magnitude than that observed with 'clamped' afferent and efferent pathways of the hormonal-sympathetic reflex. 6. A primary role for hormonal 'error signals' is presented and the impact this perspective has on past and future investigations of central mechanisms of long-term arterial pressure regulation is discussed.

Topics: Adrenergic alpha-Antagonists; Angiotensin Receptor Antagonists; Animals; Disease Models, Animal; Hormones; Hypertension; Pressoreceptors; Receptors, Angiotensin; Sodium; Sympathectomy; Sympathetic Nervous System; Time Factors; Vasopressins

Angiotensin II (ANG II) and vasopressin (AVP) act together with the mechanical effect of aortic constriction in the onset of acute aortic coarctation hypertension. Blockade of ANG II and AVP V1 receptors demonstrated that ANG II acts on the prompt (5 min) rise in pressure whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation during aortic coarctation. Hormone assays carried out on blood collected from conscious rats submitted to aortic constriction supported a role for ANG II in the early stage and a combined role for both ANG II and AVP in the maintenance of proximal hypertension. As expected, a role for catecholamines was ruled out in this model of hypertension, presumably due to the inhibitory effect of the sinoaortic baroreceptors. The lack of afferent feedback from the kidneys for AVP release from the central nervous system in rats with previous renal denervation allowed ANG II to play the major role in the onset of the hypertensive response. Median eminence-lesioned rats exhibited a prompt increase in proximal pressure followed by a progressive decline to lower hypertensive levels, revealing a significant role for the integrity of the neuroaxis in the maintenance of the aortic coarctation hypertension through the release of AVP. In conclusion, the important issue raised by this model of hypertension is the likelihood of a link between some vascular territory-probably renal-below the coarctation triggering the release of AVP, with this vasoconstrictor hormone participating with Ang II and the mechanical effect of aortic constriction in the acute aortic coarctation hypertension.

Topics: Angiotensin II; Animals; Aortic Coarctation; Dogs; Hypertension; Kidney; Rats; Renin-Angiotensin System; Vasopressins

The DNA of AVP vasopressin (AVP) is composed of 3 exons (A, B, C) and 2 introns (I, II). Following transcription, translation, and processing AVP(MW 1081) is produced. AVP receptors (VR) are classified into V1aR, V1bR and V2R. V1aR is composed of 418 amino acids (AA) and its MW is 46745. V1aR is in the vascular smooth muscle (VSM) and activates the phosphatidylinositol system, leading to the contraction of VSM. V1bR is composed of 424 AA and its MW 47034. It's second messenger systems are obscure, but V1bR is responsible for ACTH release. V2R is composed of 371 AA and its MW 40285. V2R is in the kidney and enhances the production of cAMP, leading to renal water and urea reabsorption.

Topics: Adrenocorticotropic Hormone; Animals; Blood Pressure; Body Water; Cyclic AMP; Humans; Hypertension; Receptors, Vasopressin; Second Messenger Systems; Signal Transduction; Urea; Vasopressins

Mechanisms of essential hypertension have been thought to be implicated with a number of genetic abnormalities. Those genes are closely related with vasoactive substances. On the other hand, roles of the kidney on pathogenesis of hypertension have been well recognized. Vasoactive substances and autonomic nerves influence on the renal function, particularly natriuresis. The autonomic nervous system buffers blood pressure variation caused by the vasoactive substances. But those changes in blood pressure do not usually continue for more than a day. Some other mechanisms to keep blood pressure at the higher level are necessary to maintain hypertension, which could be the resetting of baroreceptor reflex by the central nervous system. That means that vasoactive substances may act on the central nervous system. In fact, we found that almost all vasoactive substances affect central nervous system to change sympathetic nervous system activity. I reviewed the mechanism to control the long-term blood pressure level by vasoactive substances, which is related to the central nervous system.

Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Kidney; Vasopressins

The use of diuretics leads to a negative sodium and fluid balance without primary effects on serum sodium concentration. This parameter is regulated by the activity of the antidiuretic hormone (ADH) system. Secondary changes in other electrolyte systems and in acid base homeostasis also are induced by diuretic therapy. Especially diuretic induced hypokalemia is important as it is responsible for the excess mortality observed in patients with diuretic treated essential hypertension and cardiac abnormalities. All adverse metabolic effects of diuretic therapy are, in contrast to the antihypertensive action, dose dependent. Changes in fluid and electrolyte metabolism induced by diuretics occur within the first 2 or 3 weeks after initiation of medication. Counterregulatory mechanisms are activated and a new steady state is established. Serial laboratory determinations after this period are not necessary as long as this steady state is not affected by additional events (like a change in therapy or diet as well as the occurrence of vomiting or diarrhea).

Topics: Acid-Base Equilibrium; Antihypertensive Agents; Diuretics; Dose-Response Relationship, Drug; Humans; Hypertension; Hypokalemia; Risk Factors; Vasopressins; Water-Electrolyte Balance

The growing list of vasoactive substances known to be involved in blood pressure control provides new targets for antihypertensive drugs. Currently under development are alternative strategies for blockade of the renin-angiotensin system (e.g., renin inhibition and angiotensin II receptor antagonism) that may have fewer side effects than angiotensin-converting-enzyme inhibition, and antagonists to other vasocontrictor peptides, such as endothelin and vasopressin. Novel strategies to enhance the effects of endogenous vasodilators, such as natriuretic peptides and nitric oxide, are also being explored.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arginine; Endothelin Receptor Antagonists; Humans; Hypertension; Neprilysin; Renin-Angiotensin System; Vasopressins

Topics: Animals; Binding, Competitive; Blood Pressure; Bradycardia; Central Nervous System; Humans; Hypertension; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Vasopressins

Topics: Alabama; Alkalosis; Animals; Arginine Vasopressin; Awards and Prizes; Desoxycorticosterone; Drug Synergism; Female; History, 20th Century; Homeostasis; Humans; Hypertension; Hypokalemia; Kidney Tubules, Collecting; Kidney Tubules, Proximal; Male; Mice; Natriuretic Agents; Nephrology; New York; Potassium; Rabbits; Rats; Signal Transduction; Societies, Medical; Sodium; Sodium-Potassium-Exchanging ATPase; Species Specificity; Syndrome; Vasopressins; Water-Electrolyte Balance

Over the past decade several new routes of neurohypophysial hormone metabolism have been identified. These include nonhepatic splanchnic clearance and renal clearance in addition to filtration that appears to be receptor mediated. The intraluminal degradation of VP in the proximal tubule, and distal tubular secretion, at least in one species, has been identified. The brain has been identified as a site for VP and OT metabolism, and the amniotic sac may be a major site for VP clearance in the guinea pig fetus. There have been generalized findings regarding VP and OT metabolism. First, VP metabolism in the whole body and in the amniotic sac appears to increase with increasing concentrations of hormone; this does not appear to be the case with OT. Also, evidence has been presented that suggests a potential for the formation of biologically active metabolites. There have been several associations of pathophysiological states with altered VP or OT metabolism, sometimes with plasma levels remaining unchanged. Lastly, caution is emphasized when measuring these hormones by RIA, and differences in specificities of antisera toward hormone metabolites must be considered.

Topics: Animals; Female; Humans; Hypertension; Immunologic Techniques; Osmolar Concentration; Oxytocin; Pituitary Hormones, Posterior; Pregnancy; Pregnancy Complications; Vasopressins

Topics: Animals; Arginine Vasopressin; Cardiovascular Physiological Phenomena; Desoxycorticosterone; Diuresis; Female; Gonadal Steroid Hormones; Hypertension; Kidney; Male; Oxytocin; Pituitary Hormones, Posterior; Sex Characteristics; Sodium Chloride; Vasopressins

Arterial hypertension and, less often, postural hypotension are frequently associated with diabetes mellitus, and with diabetic complications and death.. To review data on the relationship between hypertension and nephropathy in diabetes mellitus.. We reviewed data on both retinopathy and nephropathy in hypertensive diabetic patients. Data suggesting that vasopressin levels might affect blood pressure in upright patients with postural hypotension due to cardiocirculatory diabetic neuropathy were also examined. Antihypertensive treatment during different phases of diabetic nephropathy in insulin-dependent diabetes was reviewed.. The data showed that hydrochlorothiazide and nitrendipine reduce urinary protein excretion in parallel with a reduction in blood pressure. However, the decreases in urinary protein excretion induced by captopril are not correlated with a reduction in blood pressure and may be related to decreases in intraglomerular pressure found in patients with mild renal failure taking furosemide. Domperidone, a peripherally acting dopaminergic antagonist is an additional therapeutic option for the treatment of diabetic postural hypotension.

Topics: Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertension, Renal; Hypotension, Orthostatic; Male; Vasopressins

Topics: Animals; Humans; Hypertension; Vasopressins

Topics: Animals; Antihypertensive Agents; Blood Pressure; Hypertension; Vasopressins

The pressor action of vasopressin (AVP) in humans was investigated with the specific anti-vasopressor V1 antagonist d(CH2)5-O(Me)-Tyr-AVP. A single 0.5-mg intravenous bolus of this agent inhibited the pressor effect of AVP by about 80%. Normally hydrated humans had no blood pressure response to this dose, but this agent did prevent the blood pressure rise in response to exogenous AVP given in doses up to 200 milli-units/kg. Patients with severe hypertension, especially that associated with end-stage renal disease, tended to respond with moderate increases in blood pressure and plasma AVP after sodium overload and had a modest blood pressure fall (10-20 mmHg) in response to a single intravenous bolus of the AVP antagonist. Patients with an impaired sympathetic nervous system had increased sensitivity to the pressor action of AVP, in keeping with knowledge derived from experimental studies. These data suggest an interaction between AVP and alpha-adrenergic function, whereby the latter tends to attenuate the pressor action of AVP although it facilitates the release of AVP in response to various stimuli. In patients with congestive heart failure, the direct pressor action of AVP appears to contribute to increased systemic vascular resistance in about 30% of cases, i.e., those with plasma AVP concentrations well above the normal range. In these subjects, circulating AVP concentrations correlated with a decrease in vascular resistance in response to the V1 antagonist.

Topics: Animals; Arginine Vasopressin; Clinical Trials as Topic; Heart Failure; Humans; Hypertension; Sympathetic Nervous System; Vasopressins

Topics: Animals; Blood Pressure; Diuresis; Dogs; Female; Hemodynamics; Homeostasis; Humans; Hypertension; Natriuresis; Rats; Vasopressins

Resistance of large arteries appears to be greater in the cerebral circulation than in other vascular beds. Large arteries contribute importantly to total cerebral vascular resistance and are major determinants of local microvascular pressure. Recent studies have shown that resistance of large arteries and cerebral microvascular pressure are affected by several physiological stimuli, including changes in systemic blood pressure, increases in cerebral metabolism, activity of sympathetic nerves, and humoral stimuli such as circulating vasopressin and angiotensin. Stimuli such as sympathetic stimulation and vasopressin produce selective responses of large arteries and, thereby, regulate microvascular pressure without a significant change in cerebral blood flow. These findings lead to the new hypothesis that the brain may be sensitive to changes in cerebral microvascular pressure, resulting in activation of compensatory neurohumoral mechanisms. Important changes occur in large cerebral arteries under pathophysiological conditions. Chronic hypertension increases resistance of large cerebral arteries, which protects the microcirculation against hypertension. Atherosclerosis potentiates constrictor responses of large cerebral arteries to serotonin and thromboxane, which may contribute to vasospasm and transient ischemic attacks.

Topics: Angiotensin II; Arterioles; Arteriosclerosis; Blood Pressure; Brain; Cerebral Arteries; Cerebrovascular Circulation; Humans; Hypertension; Ischemic Attack, Transient; Microcirculation; Sympathetic Nervous System; Thromboxanes; Vascular Resistance; Vasopressins

Topics: Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Hypertension; Natriuresis; Sodium, Dietary; Vasopressins; Water-Electrolyte Imbalance

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Blood Pressure; Humans; Hypertension; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Renin-Angiotensin System; Vasopressins

Angiotensin II (ANG II) and vasopressin (AVP) are two powerful vasoconstrictors, and atrial natriuretic peptide (ANP) is a potent vasorelaxant. The changes in the density or affinity of binding sites for these agents that may alter target organ responsiveness in hypertension are reviewed. ANG II binding in mesenteric arteries was unaltered in one-kidney, one-clip (1-K, 1-C) and in 2-K, 1-C hypertensive rats, while in deoxycorticosterone acetate (DOCA)-salt hypertensive rats ANG II binding to blood vessels was significantly increased. A role of mineralocorticoids to increase the number of vascular ANG II sites in some hypertensive models is suggested. In spontaneously hypertensive rats (SHR) ANG II receptors were increased in young rats in the prehypertensive stage with respect to Wistar-Kyoto (WKY) control rats, but normal in older rats. AVP binding in the vasculature of hypertensive rats was uniformly decreased in inverse correlation to plasma AVP levels, but vascular responsiveness to AVP was exaggerated. Inositol trisphosphate production by blood vessels of SHR in response to AVP showed that increased AVP receptor-coupled phospholipase C activity may mediate in part the exaggerated pressor response in spite of reduced or normal density of receptors for vasoconstrictor peptides. Vascular ANP sites in 2-K, 1-C, 1-K,1-C, and DOCA-salt hypertensive rats varied inversely with plasma concentrations of ANP. Normal densities of ANP receptors in saralasin-sensitive 2-K, 1-C hypertensive rats correlated with ANP sensitivity, while saralasin-insensitive 2-K, 1-C hypertensive rats, which did not respond to ANP, had significantly decreased density of ANP vascular receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Vessels; Humans; Hypertension; Receptors, Angiotensin; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Vasopressins

Topics: Animals; Blood Pressure; Heart Failure; Hemodynamics; Humans; Hypertension; Receptors, Cell Surface; Vasopressins

The vasoconstrictor actions of arginine vasopressin (AVP) have been shown to occur in concentrations much lower than previously thought. Pressor responses to AVP are a poor index of vasoconstrictor activity since, in contrast to other vasoconstrictor agents, the expected rise of pressure is offset by dose-dependent decreases of cardiac output. The mechanisms for this appear to be, in large part, modulation of the autonomic nervous system whereby AVP enhances vagal nerve activity and reduces peripheral sympathetic nerve activity. AVP enhancement of baroreceptor reflex gain is in part responsible for these changes in some species (dog and rabbit), but not in others (rat). The release of AVP appears to contribute significantly to the normalization of arterial pressure in volume-depleted and hypotensive states. The link between plasma AVP and hypertension remains unclear, but it appears likely that it has an important permissive action in the development of sodium-dependent forms of hypertension.

Topics: Animals; Autonomic Nervous System; Blood Pressure; Cats; Dogs; Female; Humans; Hypertension; Hypotension; Male; Pressoreceptors; Rats; Vasoconstrictor Agents; Vasopressins

There are several mechanisms by which the central nervous system participates in the neural and humoral alterations associated with various forms of experimental hypertension. Structures in forebrain with multiple integrative roles in neuroendocrine control of the circulation are involved. Tissue surrounding the anteroventral region of the third cerebral ventricle (AV3V region) is involved physiologically in thirst, sodium homeostasis, osmoreception, secretion of vasopressin and natriuretic factor and sympathetic discharge to blood vessels. Destruction of this tissue prevents or reverses many forms of hypertension. In genetically based spontaneous hypertension, limbic structures such as the central nucleus of the amygdala rather than the AV3V region are the necessary neuroanatomic substrate. Recent evidence suggests that a circumventricular organ in brain stem, the area postrema, is also involved in the mediation of several forms of experimental hypertension. In renin- and nonrenin-dependent forms of renal hypertension, two major factors activate central mechanisms. First, direct central actions of angiotensin, acting through receptors in the subfornical organ and organum vasculosum of the lamina terminalis, increase sympathetic discharge and secretion of vasopressin through mechanisms integrated at the level of the AV3V region. Second, sensory systems originating in the kidney can activate increased sympathetic discharge through complex projection pathways involving forebrain systems. Mineralocorticoid hypertension appears to involve enhanced secretion of vasopressin and central vasopressinergic mechanisms also dependent on the AV3V region. Reciprocal connections between key central areas involved in control of arterial pressure provide the neuroanatomical basis for central nervous system participation in hypertension.

Topics: Blood Pressure; Central Nervous System; Humans; Hypertension; Hypertension, Renal; Mineralocorticoids; Vasopressins

In this article we summarize studies of the hemodynamic and endocrine effects of desoxycorticosterone (DOC)-induced hypertension in dogs and also review new data of the action of this steroid on baroreceptors. The hemodynamic effect of subcutaneous injections of DOC to dogs, without supplementation of salt in their diet, consisted of increases in arterial pressure that were sustained for a 28-day observation period and associated with augmented cardiac output. At the early stage of the hypertensive response there was a rise in plasma Na+ concentration accompanied by increases in the plasma and cerebrospinal fluid (CSF) levels of vasopressin. The activity of the peripheral renin angiotensin system, as evaluated by the longitudinal changes in plasma renin activity and plasma immunoreactive angiotensin II (irAng-II), was markedly depressed in the hypertensive dogs. In contrast, the concentration of irAngII in the CSF did not change. Additional studies of the carotid occlusion reflex in anesthetized dogs revealed an enhanced buffering baroreceptor capacity in the early (less than day 10), but not the late (greater than day 28), stages of the hypertension. The abnormality in baroreflex function may be mediated by an effect of the steroid on an activity of brain angiotensin II that influences the inhibitory interaction between high and low pressure baroreceptors. The data acquired in these studies agree with the notion that excess mineralocorticoid production causes hypertension by mechanisms that influence the neurohormonal control of blood pressure by the central nervous system.

Topics: Angiotensin II; Animals; Desoxycorticosterone; Dogs; Hemodynamics; Hypertension; Pressoreceptors; Renin; Sodium; Vasopressins

Topics: Hormones; Humans; Hypertension; Kallikreins; Natriuretic Agents; Norepinephrine; Vasopressins

Topics: Animals; Blood Pressure; Hypertension; Vasopressins

Atriopeptins are biologically active peptides with potent natriuretic, diuretic, and vasorelaxant activities. Manipulation of an animal's salt and water intake influences the synthesis, storage, and release of atriopeptin. In addition to its direct effects on fluid and electrolyte balance, atriopeptin influences other volume regulatory hormones, including renin, aldosterone, and vasopressin. Atriopeptin, by its direct actions and its effects on hormone systems, provides a means for delicate hormonal control of fluid and electrolyte homeostasis.

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Deamino Arginine Vasopressin; Dogs; Hydroxydopamines; Hypertension; Myocardium; Oxidopamine; Rats; Rats, Inbred SHR; RNA, Messenger; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Gland Neoplasms; Aldosterone; Angiotensin II; Catecholamines; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension; Kinins; Natriuretic Agents; Pheochromocytoma; Potassium; Prostaglandins; Renin; Serotonin; Vasopressins

Data from humans and experimental animals indicate that hypertensive diseases triggered by extracellular fluid volume expansion are characterized, in their chronic phases, by relatively normal blood volume (BV) and heightened pressure-volume relationship may be viewed as corresponding to a condition of "virtual hypervolemia," where BV is inappropriately "high" relative to blood pressure. The limited data available on the phasic relationship between these variables indicate that the BV expansion appears to be a prerequisite to alterations in vascular ion metabolism, that both of these changes precede the rise in blood pressure, and that structures within the central nervous system may be a critical link between the body fluid volumes and vascular functional changes. In contrast, hypertensive diseases triggered by secretion of pressor agents or their precursors appear to be characterized in their chronic phases by low BV. These relationships and the associated alterations in plasma aldosterone and renin levels are summarized for a variety of clinical syndromes, including essential hypertension and pregnancy-induced hypertension. Direct or indirect evidence of a primary or secondary defect in renal function is apparent as an underlying event in many of these diseases.

Topics: Animals; Blood Pressure; Extracellular Space; Female; Humans; Hypertension; Kidney; Kidney Diseases; Mineralocorticoids; Pregnancy; Pregnancy Complications, Cardiovascular; Sodium Chloride; Vasopressins

The importance of the renal pressure natriuresis and diuresis mechanisms in long-term control of body fluid volumes and arterial pressure has been controversial and difficult to quantitate experimentally. Recent studies, however, have demonstrated that in several forms of chronic hypertension caused by aldosterone, angiotensin II (AngII), vasopressin, or norepinephrine and adrenocorticotropin, increased renal arterial pressure is essential for maintaining normal excretion of sodium and water in the face of reduced renal excretory capability. When renal arterial pressure was servo-controlled in these models of hypertension, sodium and water retention continued unabated, causing ascites, pulmonary edema, or even complete circulatory collapse within a few days. Apparently, other mechanisms for volume homeostasis, such as the various natriuretic and diuretic factors that have been postulated, are not sufficiently powerful to maintain fluid balance in the absence of increased renal arterial pressure when renal excretory function is reduced in these forms of hypertension. The intrarenal mechanisms responsible for pressure natriuresis and diuresis are not entirely clear, but they seem to involve small increases in glomerular filtration rate and filtered load as well as reductions in fractional reabsorption in proximal and distal tubules. During chronic disturbances of arterial pressure additional factors, especially changes in AngII and aldosterone formation, act to amplify the effectiveness of the basic renal pressure natriuresis and diuresis mechanisms in regulating arterial pressure and body fluid volumes.

Topics: Aldosterone; Angiotensin II; Animals; Blood Pressure; Diuresis; Homeostasis; Humans; Hypertension; Kidney; Natriuresis; Renin-Angiotensin System; Vasopressins

Topics: Angiotensin II; Animals; Anti-Anxiety Agents; Antihypertensive Agents; Baclofen; Benzodiazepines; Bicuculline; Blood Pressure; Brain Mapping; Cardiovascular Physiological Phenomena; Cardiovascular System; Cats; Central Nervous System; gamma-Aminobutyric Acid; Heart Rate; Hypertension; Muscimol; Rabbits; Reflex; Reticular Formation; Synaptic Transmission; Vasomotor System; Vasopressins

Recently, there has been an explosion of knowledge on vasopressin, including its neuro-anatomy, biochemistry and physiology. Recent work demonstrates extensive extra-hypothalamic vasopressinergic projections from the SON and PVN. Of particular importance are projections to the cardiovascular medullary centres. Conversely, the SON and PVN receive reciprocal catecholaminergic innervation from autonomic medullary centres. Vasopressin should now be regarded as a peptide hormone with important peripheral effects, as well as a neuropeptide acting as a neurotransmitter or neuromodulator with important CNS actions. The central and peripheral vasopressin systems are not only anatomically differentiated, but, although integrated, may also function independently. There is an important interaction between the central vasopressin system and the autonomic nervous system. Vasopressin has multiple and diverse actions on the cardiovascular system, including direct vasoconstriction, antidiuresis and hence volume control, central actions on cardiovascular neural centres, modulation of the baroreflex and direct cardiac effects. It also acts in concert with the sympathetic nervous system and the renin-angiotensin system as an integrated neurohormonal system in the control of blood pressure. Vasopressin appears to have an important role as a vasoconstrictor agent whenever volume is threatened, such as in dehydration, haemorrhage, adrenal insufficiency and orthostasis. It seems unlikely that vasopressin acts as a direct vasoconstrictor agent in the pathogenesis of any form of experimental or human hypertension. Although plasma vasopressin levels have been reported to be elevated in most forms of hypertension, this correlates best with the severity of hypertension. Furthermore, the levels are not elevated to the pressor range, so that increased vascular reactivity and sensitivity has to invoked. This does not appear to be specific for vasopressin. However, vasopressin may be indirectly involved through volume maintenance or interactions within the CNS. Indeed, its volume retaining properties have probably been underestimated. Whereas in acute situations the vasoconstrictor properties may be of some importance, it is difficult to sustain long-term hypertension without maintenance of an adequate plasma volume. Vasopressin's central actions on the cardiovascular medullary centres, the baroreflex, the autonomic nervous system and catecholamine metabolism may also be involved in some

Topics: Animals; Blood Pressure; Brain; Cardiovascular Physiological Phenomena; Heart; Humans; Hypertension; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Receptors, Angiotensin; Receptors, Vasopressin; Renin-Angiotensin System; Supraoptic Nucleus; Sympathetic Nervous System; Vasoconstriction; Vasopressins

The vasoconstrictor and vasopressor actions of vasopressin have been revealed in recent research through the use of highly specific and sensitive radioimmunoassays, employment of peptide antagonists, and comparison with an animal model which has hereditary absence of this hormone, the Brattleboro rat. Factors now known to modify the pressor effect of vasopressin are the baroreflexes, local vascular prostaglandin production, and a specific interaction with angiotensin II. In experimental models the volume retaining, but not the vasoconstrictor effect of vasopressin is necessary for mineralocorticoid-salt hypertension. Vasopressin contributes directly to the increase in arterial pressure of glycerol induced acute renal failure. In nephrectomized rats, plasma vasopressin is elevated and contributes directly to maintenance of pressure. Vasopressin antagonism may reduce arterial pressure in Goldblatt 1 and 2 kidney hypertension and in one genetic model, spontaneously hypertensive rat (SHR), but the peptide is not necessary for hypertension in these models. Plasma vasopressin is reduced in primary aldosteronism, but may be elevated in malignant hypertension. In essential hypertension, there is considerable disagreement among various studies in which plasma vasopressin, urine vasopressin excretion, platelet associated vasopressin, or vasopressin-neurophysin were measured as to whether there is evidence for increased secretion of vasopressin. Only preliminary studies of vasopressin antagonism in clinical hypertension have been reported. At present, there is no conclusive evidence that elevated vasopressin secretion occurs or is necessary for any form of clinical hypertension.

Topics: Acute Disease; Acute Kidney Injury; Animals; Central Nervous System Diseases; Desoxycorticosterone; Humans; Hypertension; Hypertension, Malignant; Hypertension, Renal; Hypertension, Renovascular; Kidney Failure, Chronic; Rats; Rats, Brattleboro; Rats, Inbred SHR; Vasopressins

The antidiuretic hormone, arginine-vasopressin (AVP), may participate in the regulation of blood pressure (BP) through its vasoconstrictor effects. In anesthetized rats, exogenous AVP induced stronger vasoconstriction in the mesenteric than in the renal vascular bed. Conversely, mesenteric but not renal vascular resistance was reduced by a vascular antagonist of AVP, d(CH2)5 VDAVP, in rats with increased endogenous AVP after anesthesia, dehydration, or injection of glycerol. Another vascular AVP-antagonist, d(CH2)5 Tyr (Me) AVP, induced a transient fall in BP in conscious primates (marmosets) after diuretic-induced volume depletion. In conscious rats with established deoxycorticosterone acetate (DOCA)/salt hypertension, d(CH2)5 Tyr (Me) AVP decreased systolic BP after acute administration. After chronic administration of this antagonist during 6 weeks after the beginning of DOCA/salt treatment, the severity of hypertension was reduced. When another, AVP-antagonist, d(CH2)5-D-Tyr (Et) VAVP, which blocks vascular and renal tubular AVP-receptors, was administered chronically, the development of DOCA/salt hypertension was prevented at the expense of severe and persistent hypernatremia. These results demonstrate that under certain conditions the vascular effects of AVP may contribute to the maintenance of BP, AVP appears to participate in the pathogenesis of DOCA/salt hypertension through both its vasoconstrictor and its antidiuretic effects.

Topics: Acute Kidney Injury; Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Glycerol; Hemodynamics; Humans; Hypertension; Kidney Tubules; Vasopressins

Anatomical studies have suggested that the posterior pituitary peptide, vasopressin (VP, antidiuretic hormone) may be released at central neural sites other than the neurohypophysis. Immunohistochemical techniques allow VP to be visualized at numerous sites in the central nervous system (CNS). VP can also be measured in cerebrospinal fluid (CSF). Some of the stimuli which evoke VP release from the posterior pituitary may also elevate CSF VP levels. VP may play an important part in a variety of CNS functions. Substantial evidence exists implicating VP in learning and memory processes. VP may have a role in cardiovascular regulation through central pathways. Further, VP appears to act on the regulation of body temperature during fever. Other areas of central regulation where VP may be important include circadian rhythmicity, control of water intake, control of permeability of brain capillaries to water, central regulation of ACTH release and nociception. It appears that at least some of these central effects of VP involve an interaction with catecholaminergic neurotransmission.

Topics: Animals; Blood-Brain Barrier; Body Temperature Regulation; Cardiovascular System; Catecholamines; Central Nervous System; Circadian Rhythm; Dogs; Hypertension; Learning; Memory; Pain; Paraventricular Hypothalamic Nucleus; Rabbits; Rats; Rats, Brattleboro; Supraoptic Nucleus; Synaptic Transmission; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Hypertension; Vasopressins

This paper will review the current state of knowledge concerning interactions between vasopressin and central neural mechanisms of cardiovascular regulation. The development of information concerning systemic cardiovascular effects of vasopressin and interactions between vasopressin and the peripheral autonomic system is outlined to provide an introduction to the topic. Major themes discussed in the rest of the paper include a survey of information suggesting direct central effects of vasopressin on autonomic control of blood pressure and heart rate and the possible localization of the central site of effect. Evidence that circulating vasopressin may act on central cardiovascular control, especially baroreflex function, is reviewed, as is the possibility of vasopressin effects on baroreflex control independent of circulating vasopressin. A survey of central pathways containing vasopressin which may be relevant to central cardiovascular actions of vasopressin is presented along with a discussion of possible regulation of activity in these pathways. Some evidence of an association between alterations in brain vasopressin levels and hypertension in experimental animals is also introduced.

Topics: Animals; Autonomic Nervous System; Brain Chemistry; Cardiovascular Physiological Phenomena; Cardiovascular System; Hypertension; Vasopressins

The association between alcohol intake and blood pressure has been known for nearly 70 years. It was postulated that the alcohol blood pressure association was not causal but linked to common factors such as stress, obesity or salt intake. Recently large population studies have shown that the association is independent of these factors. Alcohol dependent persons have a high incidence of hypertension which is a common clinical problem. It is probably due to alcohol withdrawal and is mediated via increased cortisol and catecholamine production. Alcohol has also a direct effect causing arteriolar vasoconstriction. This direct effect may result from an alcohol associated alteration of intracellular Ca in arteriolar smooth muscle leading to supersensitivity to circulating pressor agents.

Topics: Arteries; Ethanol; Hemodynamics; Humans; Hydrocortisone; Hypertension; Obesity; Renin-Angiotensin System; Sodium; Stress, Psychological; Substance Withdrawal Syndrome; Sympathetic Nervous System; Vasopressins; Water

Topics: Angiotensin II; Animals; Blood Pressure; Bradykinin; Endorphins; Hypertension; Nerve Tissue Proteins; Neurotensin; Rats; Rats, Inbred Strains; Shock; Substance P; Vasopressins

Topics: Animals; Arteries; Blood Pressure; Circadian Rhythm; Humans; Hypertension; Pressoreceptors; Rats; Rats, Mutant Strains; Vasoconstriction; Vasopressins

Elevations in the circulating levels of vasopressin within the physiological range (less than 30 fmol X mL-1) in conscious animals cause vasoconstriction of resistance vessels, the most profound effect occurring in the muscle, skin, and intestinal vascular beds. In the organism with normal baroreceptor function, the vasoconstriction is not expressed as an increase in arterial pressure because of a corresponding fall in cardiac output associated with enhanced cardiovascular reflex activity. When compensatory reflex mechanisms are impaired (baroreceptor-denervated dogs, patients with autonomic insufficiency, hypertensive rats), the vasoconstrictor activity of vasopressin is exposed and is reflected as an increase in arterial pressure. Inactivation of the vasopressin system alone by hypophysectomy or by administration of antagonists of the pressor activity of vasopressin is often accompanied by compensatory activation of the renin-angiotensin system. Thus, under certain conditions, the vasopressin system and the renin-angiotensin system operate as reciprocal or redundant mechanisms in the control of resistance vessels and of arterial pressure. In two rat models of hypertension (spontaneously hypertensive rats and DOC-salt hypertensive rats) plasma levels of vasopressin are elevated, inactivation of the vasopressin system lowers arterial pressure, and pressor responsiveness to the peptide is enhanced. The enhanced pressor responsiveness appears related in part to impaired reflex activity. The mechanism of the impaired reflexes is unknown but in spontaneously hypertensive rats it might be related to a vasopressin deficit in the paraventricular nucleus and brain stem. The evidence is consistent with the possibility that vasopressin is one factor among many that may play a role in the maintenance of arterial pressure in the adult spontaneously hypertensive rat and in the development and maintenance of the hypertensive state in DOC-salt hypertensive rats.

Topics: Angiotensin II; Animals; Blood Pressure; Desoxycorticosterone; Heart; Humans; Hypertension; Vasopressins

Topics: Angiotensin II; Animals; Dogs; Hemorrhage; Humans; Hypertension; Male; Pituitary Gland; Posture; Rats; Renin; Renin-Angiotensin System; Sodium; Supraoptic Nucleus; Thirst; Vasoconstriction; Vasopressins

Topics: Animals; Aprotinin; Bartter Syndrome; Blood Pressure; Electrolytes; Enzyme Inhibitors; Humans; Hypertension; Indomethacin; Juxtaglomerular Apparatus; Kallikreins; Kidney; Kinins; Peptidyl-Dipeptidase A; Prostaglandins; Renin; Renin-Angiotensin System; Vasopressins

Topics: Angiotensin II; Animals; Cardiac Output; Cardiomyopathies; Dogs; Hemodynamics; Homeostasis; Humans; Hypertension; Hypertension, Renal; Norepinephrine; Rabbits; Renal Artery Obstruction; Renin-Angiotensin System; Vascular Resistance; Vasopressins

Topics: Animals; Arginine Vasopressin; Blood Pressure; Blood Volume; Cardiac Output; Catecholamines; Desoxycorticosterone; Diabetes Insipidus; Drug Interactions; Hemodynamics; Hemorrhage; Homeostasis; Humans; Hypertension; Immune Sera; Pressoreceptors; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vascular Resistance; Vasopressins

Topics: Adrenal Cortex Hormones; Arrhythmias, Cardiac; Cardiovascular Diseases; Catecholamines; Cerebrovascular Disorders; Humans; Hyperglycemia; Hypertension; Hyponatremia; Models, Biological; Pulmonary Edema; Vasopressins

Topics: Animals; Calcium; Cell Membrane Permeability; Disease Models, Animal; Electric Stimulation; Hemodynamics; Humans; Hypertension; Hypothalamus; Kidney; Rabbits; Rats; USSR; Vasopressins; Water-Electrolyte Balance

The medical and social importance of hypertension, its symptoms and complications are presented. The factors of risk are examined and in particular the importance of premature onset of the hypertension in the youth is stressed. Since in teen-agers suffering from hypertension, it is probable that this disease worsen in the adult age, the necessity of a correct diagnosis and treatment also in the youth is pointed out.

Topics: Adult; Age Factors; Aged; Aldosterone; Autonomic Nervous System; Blood Pressure Determination; Bradykinin; Brain Stem; Catecholamines; Chemoreceptor Cells; Diet, Sodium-Restricted; Female; Humans; Hypertension; Male; Middle Aged; Pressoreceptors; Prostaglandins; Renin-Angiotensin System; Risk; Sex Factors; Smoking; Vasopressins

Topics: Animals; Brain; Cardiovascular Physiological Phenomena; Catecholamines; Cats; Dogs; Hemodynamics; Hypertension; Parasympathetic Nervous System; Parasympatholytics; Parasympathomimetics; Rats; Species Specificity; Vasopressins

The effects of clonidine on renal hemodynamics and renal function make it a particularly useful antihypertensive agent. During treatment of hypertensive patients with clonidine, renal blood flow and glomerular filtration rate are well maintained, and renin secretion is reduced. Early in therapy, a slight tendency to retain salt and water may be seen as blood pressure is lowered. This effect on salt and water excretion is usually transient and may be avoided if a diuretic is used concomitantly. No deterioration of renal function was noted in patients with primary hypertension who were treated with clonidine for periods from 6 months to at least 5 years. The drug is effective in patients with renal hypertension with or without renal failure and well tolerated. Clonidine is also effective in hypertensive patients undergoing chronic hemodialysis, but doses may have to be reduced because the drug is excreted chiefly by the kidney.

Topics: Adrenal Gland Neoplasms; Aldosterone; Antihypertensive Agents; Catecholamines; Clonidine; Humans; Hypertension; Kidney; Kidney Diseases; Pheochromocytoma; Renal Artery Obstruction; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Balance

Topics: Angiotensin II; Animals; Brain; Catecholamines; Disease Models, Animal; Humans; Hypertension; Hypothalamus, Anterior; Pressoreceptors; Receptors, Angiotensin; Reflex; Renin; Vasopressins

Experimental hypertensions following sino-aortic deafferentation or manoeuvres not involving initially the baroreceptor reflexes are discussed in relation with a simple graphical analysis of these reflexes. Blood pressure increases only slightly as a result of interruption of the sino-aortic afferences, but its variability is markedly enhanced. On the other hand, the final level of arterial pressure in various forms and non-neurogenic hypertension appears independent from the presence of the baroreceptor reflexes ("resetting"). Thus, the baroreceptor reflexes are of primary importance in limiting variations around a given level of arterial pressure, but they do not really set this level since it can be modified easily by other blood pressure control systems. In order to emphasize the role of the baroreflex in the short-term regulation of blood pressure and other haemodynamic variables, its significance in "whole-body autoregulation" and in the cardiovascular effects of vasopressin is discussed.

Topics: Animals; Blood Pressure; Cardiac Output; Denervation; Dogs; Feedback; Hemodynamics; Hypertension; Models, Theoretical; Pressoreceptors; Rabbits; Rats; Reflex; Sympathetic Nervous System; Vascular Resistance; Vasopressins

Present understanding of the physiology of arterial pressure regulation indicates that the renal-body fluid volume system determines the level at which the mean pressure resides over long periods of time. The relationships between blood volume, and size and compliance of the entire vascular system, and intrinsic regulation of tissue blood flow determine the sequence of observed changes in cardiac output and total peripheral resistance. Current evidence is compatible with the concept that functional changes in the renal vasculature or tubular system, either intrinsic or extrinsic in origin, reflect the final common pathway in the genesis of all forms of experimental and human hypertension. At the present time the nature of these renal changes appears to alter the fundamental relationships between renal perfusion pressure and sodium and water excretion. One of the major challenges in the field of hypertension today is to test the hypothesis that changes in renal function, either extrinsic or intrinsic in form, are involved in all forms of hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Blood Vessels; Body Water; Cardiac Output; Chemoreceptor Cells; Dogs; Heart; Humans; Hypertension; Kidney; Male; Mechanoreceptors; Rats; Reflex; Renin; Vascular Resistance; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Blood Proteins; Blood Vessels; Carotid Arteries; Cats; Dogs; Dose-Response Relationship, Drug; Drug Interactions; Epinephrine; Glucocorticoids; Guinea Pigs; Hindlimb; Hypertension; Hypertension, Renal; Kidney; Mineralocorticoids; Norepinephrine; Prostaglandins; Rabbits; Rats; Regional Blood Flow; Retinal Vessels; Saphenous Vein; Serotonin; Vasoconstrictor Agents; Vasopressins

Topics: Adrenal Gland Diseases; Adrenal Glands; Adrenalectomy; Cushing Syndrome; Dexamethasone; Diagnosis, Differential; Humans; Hydrocortisone; Hyperaldosteronism; Hypertension; Hypokalemia; Kidney; Obesity; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Vasopressins

Topics: Aldosterone; Angiotensin II; Edema; Extracellular Space; Female; Glomerular Filtration Rate; Humans; Hyperaldosteronism; Hypertension; Hypotension; Juxtaglomerular Apparatus; Kidney; Kidney Diseases; Kidney Failure, Chronic; Natriuresis; Potassium; Pregnancy; Pregnancy Complications; Pressoreceptors; Regional Blood Flow; Renal Artery Obstruction; Renin; Vasopressins

Topics: Adrenalectomy; Angiotensin II; Animals; Blood Pressure; Body Weight; Catecholamines; Desoxycorticosterone; Female; Growth Hormone; Hippocampus; Hypertension; Hypophysectomy; Methylprednisolone; Norepinephrine; Rats; Reticular Formation; Sensory Deprivation; Sound; Tyramine; Vasopressins

Topics: Adrenal Cortex Hormones; Animals; Biopsy; Body Weight; Diet, Sodium-Restricted; Eclampsia; Edema; Female; Glomerulonephritis; Humans; Hypertension; Hypertension, Renal; Kidney; Kidney Diseases; Nephritis; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pyelonephritis; Sodium; Uric Acid; Vasopressins; Water-Electrolyte Balance

Topics: Angiography; Biological Transport, Active; Contrast Media; Dehydration; Diuresis; Furosemide; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Calculi; Kidney Concentrating Ability; Kidney Failure, Chronic; Kidney Tubules; Male; Metaraminol; Prostatic Diseases; Renal Artery Obstruction; Sodium; Urinary Calculi; Urography; Vasopressins

Topics: Acute Kidney Injury; Aminohippuric Acids; Animals; Blood Flow Velocity; Calorimetry; Dogs; Glomerular Filtration Rate; Hemodynamics; Humans; Hydrogen; Hypertension; Indicator Dilution Techniques; Indicators and Reagents; Kidney; Krypton; Regional Blood Flow; Renin; Sodium; Vasopressins

Topics: Aldosterone; Angiotensin II; Animals; Arteriovenous Anastomosis; Cardiac Volume; Catecholamines; Diuretics; Heart Failure; Hemodynamics; Hypertension; Kidney; Kidney Tubules; Oxygen; Sodium; Vascular Resistance; Vasomotor System; Vasopressins; Veins; Water-Electrolyte Balance

Topics: Aldosterone; Angiotensin II; Aorta; Carotid Sinus; Humans; Hypertension; Hypothalamus; Juxtaglomerular Apparatus; Kidney; Pressoreceptors; Renin; Sympathetic Nervous System; Vasopressins; Water-Electrolyte Balance

Topics: Aldosterone; Angiotensins; Blood Circulation; Blood Vessels; Blood Viscosity; Blood Volume; Blood Volume Determination; Carotid Sinus; Chromium Isotopes; Epinephrine; Erythropoiesis; Guanethidine; Hypertension; Hypoxia; Iodine Isotopes; Kinins; Pharmacology; Renin; Research; Sensory Receptor Cells; Serotonin; Vasodilator Agents; Vasomotor System; Vasopressins

Topics: Adrenal Glands; Aldosterone; Angiotensins; Arteriosclerosis; Autonomic Nervous System Diseases; Catecholamines; Chromosome Aberrations; Essential Hypertension; Hypertension; Metabolism; Nephrectomy; Obesity; Sodium; Thyroid Gland; Vasopressins; Water-Electrolyte Balance

Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension.. We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2(CR), u-ENaC(β-CR)), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day).. At baseline, no differences in u-AQP2(CR) or u-ENaC(β-CR) were measured between patients and controls. U-AQP2(CR) increased significantly more after saline in patients than controls, whereas u-ENaC(β-CR) increased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2(CR) response.. No differences were found in u-AQP2(CR) and u-ENaC(β-CR) between patients and controls at baseline. However, in response to saline, u-AQP2(CR) was abnormally increased in patients, whereas the u-ENaC(β-CR) response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent. Clinicaltrial.gov identifier: NCT00345124.

Topics: Adult; Aldosterone; Angiotensin II; Aquaporin 2; Atrial Natriuretic Factor; Cross-Over Studies; Cyclic AMP; Dinoprostone; Epithelial Sodium Channels; Female; Glomerular Filtration Rate; Humans; Hypertension; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Osmolar Concentration; Renin; Sodium; Sodium, Dietary; Vasopressins

Magnesium is well known to inhibit catecholamine release and attenuate vasopressin-stimulated vasoconstriction. We investigated whether i.v. magnesium sulphate attenuates the haemodynamic stress responses to pneumoperitoneum by changing neurohumoral responses during laparoscopic cholecystectomy.. Thirty-two patients undergoing laparoscopic cholecystectomy were randomly assigned to two groups; a control group was given saline, and a magnesium group received magnesium sulphate 50 mg kg(-1) immediately before pneumoperitoneum. Arterial pressure, heart rate, serum magnesium, plasma renin activity (PRA), and catecholamine, cortisol, and vasopressin levels were measured.. Systolic and diastolic arterial pressures were greater in the control group (P<0.05) than in the magnesium group at 10, 20, and 30 min post-pneumoperitoneum. Norepinephrine or epinephrine levels [pg ml(-1), mean (SD)] were higher in the control group than in the magnesium group at 5 [211 (37) vs 138 (18)] or 10 min [59 (19) vs 39 (9)] post-pneumoperitoneum, respectively (P<0.05). In the control group, vasopressin levels [pg ml(-1), mean (SD)] were higher compared with the magnesium group at 5 [64 (18) vs 35 (9), P<0.01] and 10 min [65 (18) vs 47 (11), P<0.05] post-pneumoperitoneum. There were no significant differences between the groups in PRA and cortisol levels.. I.V. magnesium sulphate before pneumoperitoneum attenuates arterial pressure increases during laparoscopic cholecystectomy. This attenuation is apparently related to reductions in the release of catecholamine, vasopressin, or both.

Topics: Adult; Anesthesia, General; Antihypertensive Agents; Blood Pressure; Cholecystectomy, Laparoscopic; Double-Blind Method; Epinephrine; Female; Heart Rate; Humans; Hydrocortisone; Hypertension; Injections, Intravenous; Intraoperative Complications; Magnesium Sulfate; Male; Middle Aged; Norepinephrine; Pneumoperitoneum, Artificial; Renin; Vasopressins

Survival rates for cardiac arrest patients, both in and out of hospital, are poor. Results of a previous study suggest better outcomes for patients treated with vasopressin than for those given epinephrine, in the out-of-hospital setting. Our aim was to compare the effectiveness and safety of these drugs for the treatment of in-patient cardiac arrest.. We did a triple-blind randomised trial in the emergency departments, critical care units, and wards of three Canadian teaching hospitals. We assigned adults who had cardiac arrest and required drug therapy to receive one dose of vasopressin 40 U or epinephrine 1 mg intravenously, as the initial vasopressor. Patients who failed to respond to the study intervention were given epinephrine as a rescue medication. The primary outcomes were survival to hospital discharge, survival to 1 h, and neurological function. Preplanned subgroup assessments included patients with myocardial ischaemia or infarction, initial cardiac rhythm, and age.. We assigned 104 patients to vasopressin and 96 to epinephrine. For patients receiving vasopressin or epinephrine survival did not differ for hospital discharge (12 [12%] vs 13 [14%], respectively; p50.67; 95% CI for absolute increase in survival 211.8% to 7.8%) or for 1 h survival (40 [39%] vs 34 [35%]; p50.66; 210.9% to 17.0%); survivors had closely similar median mini-mental state examination scores (36 [range 19-38] vs 35 [20-40]; p50.75) and median cerebral performance category scores (1 vs 1).. We failed to detect any survival advantage for vasopressin over epinephrine. We cannot recommend the routine use of vasopressin for inhospital cardiac arrest patients, and disagree with American Heart Association guidelines, which recommend vasopressin as alternative therapy for cardiac arrest.

Topics: Aged; Arrhythmias, Cardiac; Cognition Disorders; Double-Blind Method; Epinephrine; Female; Heart Arrest; Hospitalization; Humans; Hypertension; Infarction; Male; Mental Status Schedule; Mesentery; Middle Aged; Ontario; Resuscitation; Safety; Survival Analysis; Time Factors; Treatment Outcome; Vasopressins

To study the role of vasopressin (VP) in essential hypertension, we examined plasma levels of VP and blood pressure (BP) response to an orally active V1 receptor antagonist, OPC-21268, in hypertensive patients on diets with different sodium contents. Plasma VP was determined in 12 normotensive subjects and 12 patients with mild essential hypertension on a regular sodium diet, and in eight hypertensive patients on a high sodium (250 mmol/day) and a low sodium (25 mmol/day) diet. BP response was examined for 4 h after single oral administration of OPC-21268 (100 mg) or placebo in eight patients on the regular diet, and in six patients on the high and low sodium diets. In four patients on the regular diet, the effects of OPC-21268 on the baroreflex control of heart rate were also examined with intravenous injections of methoxamine. Plasma VP did not differ between the normotensive and hypertensive subjects. Levels of VP in the plasma was higher in the high sodium than in the low sodium period, but the difference was not significant. BP and heart rate did not change significantly after administration of OPC-21268 or placebo under either condition. OPC-21268 also failed to lower BP in salt-sensitive patients on the high sodium diet. The baroreceptor reflex sensitivity was not modified by the administration of OPC-21268. Our results suggest that VP does not play an important role in mild essential hypertension through its action on the V1 receptors regardless of dietary sodium intake.

Topics: Adult; Aged; Antidiuretic Hormone Receptor Antagonists; Baroreflex; Blood Pressure; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Piperidines; Quinolones; Sodium, Dietary; Vasopressins

Two groups of subjects (uraemic and control) were studied. The uraemic group consisted of 30 patients treated by HD (haemodialysis). The mean age was x +/- SD-35.4 +/- 8.4 years, duration of haemodialysis treatment 42.8 +/- 12.1 months, cuprophan dialyzers and acetate containing solution--35 mEq/l--were used, duration of HD-4 hours 3 times weekly, predialysis serum creatinine was 1060 +/- 218 mumol/l (12.8 +/- 2.5 mg%). The control group comprised 23 healthy subjects (mean age 33.0 +/- 8.0 years, serum creatinine level 88.4 +/- 14 mumol/l (1.0 +/- 0.16 mg%). In all examined subjects the following experimental protocol was used. Blood pressure (BP) was determined at about 8 a.m. after an overnight rest. Then blood samples were withdrawn for estimation of ANP, AVP, sodium and potassium, protein, osmolality and creatinine concentrations. Between 8 and 12 a.m. all examined uraemic subjects were dialysed. After each hour of dialysis BP was measured and blood samples were taken. ANP (Peninsula Lab. Kids.) and AVP (DRG) were measured using RIA method, and other biochemical parameters using routine methods. Plasma creatinine and plasma ANP levels significantly decreased, but AVP significantly increased after HD.. 1. In all uraemic subjects, plasma ANP and AVP levels were significantly higher than in control subjects; 2. During haemodialysis with ultrafiltration a significant increase AVP level and decrease ANP level was observed; 3. A significant correlation between ANP concentration and blood pressure may suggest participation of above mentioned hormone in pathogenesis of hypertension in patients with uraemia; 4. It's possible, in pathogenesis plasma AVP increase takes part plasma ANP decrease, too.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Humans; Hypertension; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Vasopressins

Acute hypertensive responses during nitrous oxide-opioid-relaxant anesthesia are a common clinical problem. In adult men undergoing radical prostatectomy procedures and anesthetized with a standardized technique, we evaluated the effectiveness of alfentanil, isoflurane, and trimethaphan in treating acute hemodynamic and stress hormone responses to surgical stimulation. Stress hormone concentrations were measured 1 min before skin incision, after the onset of an acute hypertensive response, and after returning the mean arterial pressure to within 10% of the preincision values with one of the three treatment modalities. Pretreatment plasma alfentanil concentrations (151 +/- 47 to 156 +/- 47 ng.ml-1) and end-tidal nitrous oxide concentrations (66 +/- 2 to 68 +/- 2%) were similar in all three groups. Acute hypertensive events were associated with significantly increased concentrations of catecholamines and vasopressin (antidiuretic hormone [ADH]). Whereas intravenous alfentanil returned all hormone concentrations to preincision values, norepinephrine and glucose concentrations were significantly increased after adjunctive isoflurane administration. Although trimethaphan decreased the norepinephrine concentration, the epinephrine, beta-endorphin, cortisol, ADH, and glucose concentrations were significantly increased compared to preincision values. However, the persistent elevation in the posttreatment ADH concentration in the trimethaphan group was the only significant difference between the three groups. Mean (+/- standard deviation) times to awakening (2.8 +/- 3.3 to 3.8 +/- 4.2 min), extubation (8.1 +/- 4.8 to 10.3 +/- 8.5 min), and orientation (19.6 +/- 20.4 to 24.6 +/- 19.1 min) were similar in all three groups. Naloxone was required more frequently in patients in the alfentanil (35%) and isoflurane (24%) groups than in the trimethaphan group (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Alfentanil; Anesthesia, General; Blood Pressure; Epinephrine; Heart Rate; Humans; Hypertension; Intraoperative Complications; Isoflurane; Male; Middle Aged; Nitrous Oxide; Norepinephrine; Prostatectomy; Single-Blind Method; Trimethaphan; Vasopressins; Vecuronium Bromide

Cardiovascular and hormonal responses to reconstructive abdominal aortic surgery were studied in 20 patients anaesthetized either with moderate-dose fentanyl (20 micrograms kg-1) combined with isoflurane, nitrous oxide and oxygen (n = 10), or with thoracolumbar epidural bupivacaine combined with isoflurane, nitrous oxide and oxygen (n = 10). After the start of operation, hypotension occurred in four patients in the epidural group. In both groups, the aortic cross-clamping caused slight increases both in mean arterial pressure and in calculated systemic vascular resistance, and a significant decrease in cardiac index. At the same time, a marked increase in plasma vasopressin was seen in the fentanyl group. Plasma catecholamines were low in both groups. After aortic declamping, the cardiac index improved in both groups, although two patients in the fentanyl group and four patients in the epidural group were hypotensive. Post-operatively, eight patients in the fentanyl group were hypertensive, versus none in the epidural group, in which bupivacaine-fentanyl was administered epidurally. At the same time, plasma vasopressin and adrenaline increased significantly in both groups, whereas plasma noradrenaline did so only in the fentanyl group. The results suggest that thoracolumbar epidural bupivacaine combined with low-dose isoflurane in nitrous-oxide-oxygen prevents intra-operative hypertension and tachycardia, but it may cause hypotension. Post-operative hypertension and tachycardia as well as the increase in plasma noradrenaline are prevented by epidural administration of bupivacaine-fentanyl.

Topics: Aged; Anesthesia, Epidural; Anesthesia, Inhalation; Anesthesia, Intravenous; Aorta, Abdominal; Blood Pressure; Bupivacaine; Cardiac Output; Female; Fentanyl; Fluid Therapy; Heart Rate; Humans; Hypertension; Hypotension; Intraoperative Complications; Isoflurane; Male; Middle Aged; Norepinephrine; Pain, Postoperative; Postoperative Complications; Tachycardia; Vascular Resistance; Vasopressins

A study was carried out of 22 patients with essential hypertension who were treated with metoprolol (100 mg/day) and placebo for 4 weeks. Felodipine (n = 11) or prazosin (n = 11) were then added in increasing doses (felodipine 5, 10, 20 mg bid; prazosin 1, 2, 4 mg bid) for 2 weeks until a diastolic blood pressure of less than or equal to 90 mm Hg was achieved. Acute haemodynamic and hormonal responses to 80 degrees tilting (measurements after 4 minutes' tilt) were obtained immediately prior to randomisation to felodipine or prazosin, and after 6 to 8 weeks of treatment. At randomisation, 80 degrees tilt produced no change in blood pressure and only a small increase in pulse rate. There was no significant change in the plasma renin-angiotensin system, vasopressin or adrenaline concentrations. Plasma noradrenaline concentration rose in response to 80 degrees tilt. Following substitution of felodipine (n = 11) or prazosin (n = 11) for placebo, and continuation of metoprolol, blood pressure fell. 80 degrees tilt caused no change in the plasma renin-angiotensin system, vasopressin or adrenaline concentration. Plasma noradrenaline concentration rose in response to tilt, as before. Felodipine is an effective antihypertensive agent when used with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin II; Antihypertensive Agents; Blood Pressure; Catecholamines; Felodipine; Female; Humans; Hypertension; Male; Middle Aged; Nitrendipine; Prazosin; Pulse; Renin; Vasopressins

In 22 50-year-old men with long-standing, untreated essential hypertension of the low renin type, venous plasma vasopressin concentrations were about three times those of 15 matched normotensive control subjects (p less than 0.005). These patients also had increased arterial concentrations of noradrenaline and adrenaline (p less than 0.05) but there was no direct association between these two catecholamines and vasopressin. On the other hand, adrenergic beta-receptor blockade with oxprenolol reduced both blood pressure and plasma vasopressin (p less than 0.01) while venous plasma dopamine concentrations significantly increased. In addition, the hypertensives had highly significantly increased serum uric acid (p less than 0.001) that correlated positively with venous vasopressin concentrations (p less than 0.05). According to these data, patients with the volume-sustained low renin type of essential hypertension have increased plasma vasopressin concentrations that probably are inversely related to dopaminergic nervous activity. The data also indicate that increased plasma vasopressin correlates with serum uric acid, most probably through increased tubular reabsorption of this acid.

Topics: Atenolol; Blood Pressure; Body Weight; Catecholamines; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxprenolol; Renin; Uric Acid; Vasopressins

The effects of 0.5 mg of slow-release (sr) clonidine, 800 mg of acebutolol, and of both drugs combined on blood pressure and the water-salt balance were compared in 10 patients with essential hypertension. An initial placebo period was followed by three 72-h periods during which 5 patients were given sr-clonidine, acebutolol plus sr-clonidine, and acebutolol, respectively in that order whereas the other 5 received the same drugs in the opposite order. Placebo and active medications were given once a day, and the recorded variables were measured 24 h after the last intake. Sr-clonidine, acebutolol and their combined administration reduced mean blood pressure by 23, 16 and 39 mmHg, respectively, indicating first, that single daily doses of sr-clonidine and/or acebutolol constitute satisfactory antihypertensive treatments and second, that the interaction of these drugs is additive. All three treatments reduced plasma renin activity significantly and similarly. A reduction in plasma and urinary aldosterone was observed with sr-clonidine, and a decrease in plasma noradrenaline with the combined treatment. Both water diuresis and natriuresis rose significantly during combined therapy. The additive antihypertensive effects of sr-clonidine and acebutolol might be due to the parallel inhibition observed in the renin and sympathetic systems, and to the increase in natriuresis.

Topics: Acebutolol; Adult; Blood Pressure; Clinical Trials as Topic; Clonidine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Norepinephrine; Random Allocation; Renin-Angiotensin System; Vasopressins; Water-Electrolyte Balance

In a double-blind versus placebo preliminary study conducted in seven mildly hypertensive patients, the 10-mg capsule form of nifedipine was able to reduce significantly systolic and diastolic blood pressure (-14%) for 3 h. In a single-dose, cross-over study, captopril (1 mg/kg) and nifedipine (20 mg) significantly reduced blood pressure in 12 patients with moderate essential hypertension, but the mean maximum arterial pressure reduction was faster and greater with nifedipine than with captopril (-23 +/- 2% at 37 +/- 15 min and -17 +/- 1% at 86 +/- 25 min, respectively). Nifedipine did not significantly alter the renin angiotensin aldosterone system in supine and upright positions, and the blood pressure drop it induced was not related to the initial level of activation of that system. Associated with the stimulation of the sympathetic nervous system, an increased release of vasopressin was noted during nifedipine administration. Finally, nifedipine, a calcium antagonist, was a potent antihypertensive drug through its vasodilating properties. It provoked specific hormonal alterations, i.e., stimulation of catecholamines and vasopressin release, whereas the renin angiotensin aldosterone system was not significantly altered.

Topics: Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Hormones; Humans; Hypertension; Nifedipine; Renin-Angiotensin System; Time Factors; Vasopressins

In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W.H.O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: -23 +/- 2% at 37 +/- 15 min and -17 +/- 1% at 86 +/- 25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.

Topics: Administration, Oral; Adult; Aged; Aldosterone; Captopril; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Proline; Pyridines; Renin; Renin-Angiotensin System; Vasopressins

Topics: Adult; Aged; Captopril; Clinical Trials as Topic; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Proline; Pyridines; Vasopressins

Topics: Adult; Aldosterone; Angiotensin II; Clinical Trials as Topic; Contraceptives, Oral; Ethinyl Estradiol; Female; Humans; Hypertension; Male; Middle Aged; Renin; Sodium Chloride; Vasopressins; Water

Among hypertensive patients, plasma renin activity is lower and the response to diuretic monotherapy greater in volume responsive hypertensive patients. We hypothesized that hormones influencing extracellular volume such as vasopressin / antidiuretic hormone (ADH) might permit the development of a simple test to identify those with volume-related hypertension. Such a test might be of particular benefit to the Black population which is purported to have a higher incidence of volume-related and responsive hypertension. Thus, using copeptin, a surrogate marker for ADH, we studied if there were differences in this hormone between those with and without volume responsive hypertension.. Serum copeptin was measured in biobanked blood samples from the Genetic Epidemiology of Responses to Antihypertensives (GERA) I study and analyzed with other variables from the study dataset.. There was no relationship between PRA and copeptin values nor could the response in blood pressure be predicted by the copeptin values. However, baseline copeptin levels were higher in Black than in White subjects (7.5 pmol/L vs 5.4 pmol/L, P < 0.001) while plasma sodium and calculated plasma osmolality were slightly lower in keeping with the concept that Black subjects have more volume-related hypertension. In addition, after hydrochlorothiazide (HCTZ), copeptin was significantly lower in Black (6.2 pmol/L, P = 0.004) but unchanged in White subjects (5.2 pmol/L, P = 0.901) and there were also changes in sodium.. The current study suggests differences in ADH physiology between hypertensive Black and White patients. However, the use of copeptin to identify volume responsive patients could not be confirmed.

Topics: Biomarkers; Glycopeptides; Humans; Hypertension; Sodium; Vasopressins

Chronic high salt intake is one of the leading causes of hypertension. Salt activates the release of the key neurotransmitters in the hypothalamus such as vasopressin to increase blood pressure, and neuropepetide Y (NPY) has been implicated in the modulation of vasopressin levels. NPY in the hypothalamic arcuate nucleus (Arc) is best known for its control in appetite and energy homeostasis, but it is unclear whether it is also involved in the development of salt-induced hypertension. Here, we demonstrate that wild-type mice given 2% NaCl salt water for 8 weeks developed hypertension which was associated with marked downregulation of NPY expression in the hypothalamic Arc as demonstrated in NPY-GFP reporter mice as well as by in situ hybridization analysis. Furthermore, salt intake activates neurons in the hypothalamic paraventricular nucleus (PVN) where mRNA expression of brain-derived neurotrophic factor (BDNF) and vasopressin was found to be upregulated, leading to elevated serum vasopressin levels. This finding suggests an inverse correlation between the Arc NPY level and expression of vasopressin and BDNF in the PVN. Specific restoration of NPY by injecting AAV-Cre recombinase into the Arc only of the NPY-targeted mutant mice carrying a loxP-flanked STOP cassette reversed effects of salt intake on vasopressin and BDNF expression, leading to a normalization of salt-dependent blood pressure. In summary, our study uncovers an important Arc NPY-originated neuronal circuitry that could sense and respond to peripheral electrolyte signals and thereby regulate hypertension via vasopressin and BDNF in the PVN.

Topics: Animals; Brain-Derived Neurotrophic Factor; Hypertension; Mice; Neuropeptide Y; Sodium Chloride; Sodium Chloride, Dietary; Vasopressins

Topics: Blood Pressure; Humans; Hypertension; Male; Sodium Chloride; Sodium Chloride, Dietary; Vasopressins

High dietary salt increases arterial pressure partly through activation of magnocellular neurosecretory cells (MNC

Topics: Angiotensin II; Animals; Cell Membrane; Cytoskeleton; Disease Models, Animal; Excitatory Postsynaptic Potentials; Hypertension; Male; Mechanotransduction, Cellular; Neurons; Osmosis; Probability; Rats, Wistar; Sodium Chloride, Dietary; Synapses; Vasopressins

Topics: Adrenergic beta-Antagonists; Amputation, Surgical; Cefepime; Child; Clindamycin; Debridement; Diagnosis, Differential; Epinephrine; Fasciotomy; Female; Fluid Therapy; Humans; Hypertension; Ischemia; Leg; Norepinephrine; Propranolol; Shock, Septic; Tachycardia; Therapeutic Irrigation; Treatment Outcome; Vasopressins

In the brain, aminopeptidase A (APA) generates angiotensin III, one of the effector peptides of the brain renin-angiotensin system (RAS), exerting tonic stimulatory control over blood pressure (BP) in hypertensive rats. Oral administration of firibastat, an APA inhibitor prodrug, in hypertensive rats, inhibits brain APA activity, blocks brain angiotensin III formation and decreases BP. In this study, we evaluated the efficacy of firibastat in combination with enalapril, an angiotensin I-converting enzyme inhibitor, and hydrochlorothiazide (HCTZ), in conscious hypertensive deoxycorticosterone acetate (DOCA)-salt rats, which display high plasma arginine-vasopressin levels, low circulating renin levels and resistance to treatment by systemic RAS blockers. We determined mean arterial BP, heart rate, plasma arginine-vasopressin levels and renin activity in DOCA-salt rats orally treated with firibastat, enalapril or HCTZ administered alone or in combination. Acute oral firibastat administration (30 mg/kg) induced a significant decrease in BP, whereas enalapril (10 mg/kg) or HCTZ (10 mg/kg) administered alone induced no significant change in BP in conscious DOCA-salt rats. The BP decrease induced by acute and nine-day chronic tritherapy [Firibastat+Enalapril+HCTZ] was significantly greater than that observed after bitherapy [Enalapril+HCTZ]. Interestingly, the chronic administration of a combination of firibastat with [Enalapril+HCTZ] reduced plasma arginine-vasopressin levels by 62% relative to those measured in DOCA-salt rats receiving bitherapy. Our data show that tritherapy with firibastat, enalapril and HCTZ improves BP control and arginine-vasopressin release in an experimental salt-dependent model of hypertension, paving the way for the development of new treatments for patients with currently difficult-to-treat or resistant hypertension.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Desoxycorticosterone Acetate; Disease Models, Animal; Disulfides; Enalapril; Glutamyl Aminopeptidase; Hydrochlorothiazide; Hypertension; Male; Rats; Rats, Inbred WKY; Renin-Angiotensin System; Sulfonic Acids; Vasopressins

The aim of this work was to study the effect of a high sodium (HS) diet on blood pressure and renal function in male adult rats that have been treated with a dual Endothelin receptor antagonist (ERA) during their early postnatal period (day 1 to 20 of life). Male Sprague-Dawley rats were divided in four groups: CNS: control rats with normosodic diet; ERANS: ERA-treated rats with normosodic diet; CHS: control rats with high sodium diet; ERAHS: ERA-treated rats with HS diet. Systolic blood pressure (SBP) was recorded before and after the diet and 24-hour metabolic cage studies were performed. AQP2 and α-ENac expressions were measured by western blot and real time PCR in the renal medulla. Vasopressin (AVP) pathway was evaluated by measuring V2 receptor and adenylyl cyclase 6 (AC6) expression and cAMP production in the renal medulla. Pre-pro ET-1mRNA was also evaluated in the renal medulla. Only rats that had been treated with an ERA during their postnatal period increased their SBP after consumption of a HS diet, showing an impaired capacity to excrete sodium and water, i.e. developing salt sensitivity. This salt sensitivity would be mediated by an increase in renomedullary expression and activity of AQP2 and α-ENaC as a consequence of increased AC6 expression and cAMP production and/or a decreased ET-1 production in the renal medulla. The knowledge of the molecular mechanisms underlying the perinatal programming of salt sensitive hypertension will allow the development of reprogramming strategies in order to avoid this pathology.

Topics: Adult; Animals; Animals, Newborn; Aquaporin 2; Blood Pressure; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelins; Epithelial Sodium Channels; Humans; Hypertension; Infant, Newborn; Kidney Medulla; Male; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Renal Elimination; Signal Transduction; Sodium Chloride, Dietary; Vasopressins

Vasopressin (VP) is a neurohypophyseal peptide best known for its role in maintaining osmotic and cardiovascular homeostasis. The main sources of VP are the supraoptic and paraventricular (PVN) nuclei of the hypothalamus, which coexpress the vasopressin V1a and V1b receptors (V1aR and V1bR). Here, we investigated the level of expression of VP and VP receptors in the PVN of borderline hypertensive rats (BHRs), a key integrative nucleus for neuroendocrine cardiovascular control. Experiments were performed in male BHRs and Wistar rats (WRs) equipped with a radiotelemetry device for continuous hemodynamic recording under baseline conditions and after saline load without or with stress. Autonomic control of the circulation was evaluated by spectral analysis of blood pressure (BP) and heart rate (HR) variability and baroreceptor reflex sensitivity (BRS) using the sequence method. Plasma VP was determined by radioimmunoassay, and VP, V1aR, and V1bR gene expression was determined by RT-qPCR. Under baseline conditions, BHRs had higher BP, lower HR, and stronger BRS than WRs. BP and HR variability was unchanged. In the PVN, overexpression of the VP and V1bR genes was found, and plasma VP was increased. Saline load downregulated V1bR mRNA expression without affecting VP mRNA expression or plasma VP and BP. Adding stress increased BP, HR, and low-frequency sympathetic spectral markers and decreased plasma VP without altering the level of expression of VP and VP receptors in the PVN. It follows that overexpression of VP and V1bR in the PVN is a characteristic trait of BHRs and that sympathetic hyperactivity underlies stress-induced hypertension.

Topics: Animals; Baroreflex; Crowding; Female; Hypertension; Male; Paraventricular Hypothalamic Nucleus; Random Allocation; Rats, Inbred SHR; Rats, Wistar; Receptors, Vasopressin; Stress, Psychological; Vasopressins

Recent evidence suggests that elevated plasma levels of Trimethylamine-N-oxide (TMAO) can prolong the duration of elevated blood pressure in rats. The purpose of this study was to investigate the plasma TMAO level in Spontaneously Hypertensive Rats (SHR) and to explore the possible relationship between TMAO and aquaporin-2 (AQP-2) in the formation of hypertension. Twelve-week-old, male Spontaneously Hypertensive rats (SHR, n = 40) and Wistar-Kyoto rats (WKY, n = 40) were accordingly grouped into SHR group and WKY group. Each group was divided randomly into four subgroups: Untreated group, TMAO group, TMAO+Tolvaptan (TMAO+TVP) group, and TVP group, respectively. Systolic blood pressure (SBP), plasma TMAO, plasma osmolality (POsm), plasma vasopressin (PAVP), and plasma AQP-2 (PAQP-2) concentration were measured, and the expression of AQP-2 in kidney medulla was detected by RT-PCR and Western blot. At 14 weeks, rats in SHR TMAO group were shown the increased plasma TMAO, POsm, PAVP, and PAQP-2 levels, while those rats in SHR TMAO+TVP group were shown the decreased plasma TMAO, POsm, and PAQP-2 levels, but an even higher PAVP (due to the blockage of TVP to V2 receptor). These findings indicate that an increase of plasma TMAO levels in SHR leads to a higher plasma osmotic pressure, triggers the regulation of the TMAO-AVP-AQP-2 axis in SHR, elicits the greater water reabsorption, and eventually leads to hypertension.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Blood Pressure; Hypertension; Kidney Medulla; Male; Methylamines; Osmolar Concentration; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Tolvaptan; Vasopressins

Hypertension and baroreflex dysfunction confer poorer outcomes in patients with polycystic kidney disease (PKD).. We examined whether hypothalamic paraventricular nucleus (PVN) activation or circulating vasopressin contribute to hypertension and baroreflex dysfunction in the Lewis polycystic kidney (LPK) rat.. Bilateral PVN inhibition with muscimol reduced SBP further in urethane-anaesthetized adult LPK rats than in control Lewis rats (-43 ± 4 vs. -18 ± 3 mmHg; P < 0.0001, n = 14), but was not associated with a greater reduction in sympathetic nerve activity (SNA) or improvement in HR or SNA baroreflex function. Blockade of ionotropic glutamatergic input to the PVN with kynurenic acid also reduced SBP (P < 0.001), but not SNA, further in both adult and juvenile LPK rats. No differences in AMPA or NMDA receptor mRNA expression were noted. Systemic V1A receptor antagonism using OPC-21268 reduced SBP in adult LPK rats only (P < 0.001) and had no effect on the depressor response to PVN inhibition (P = 0.39). Combined peripheral V1A receptor antagonism and PVN inhibition, however, normalized SBP in adult LPK rats (122 ± 11 vs. 115 ± 6 mmHg; LPK vs. Lewis, P > 0.05, n = 10).. Our data show that in the LPK rat model of PKD, hypertension is contributed to by increased PVN neuronal activity and, through an independent mechanism, systemic V1A receptor activation. Treatments that reduce PVN neuronal activity and/or inhibit peripheral V1A receptors may provide novel treatment strategies to ameliorate hypertension in individuals with PKD and limit overall disease progression.

Topics: Animals; Disease Models, Animal; Hypertension; Paraventricular Hypothalamic Nucleus; Polycystic Kidney Diseases; Rats; Vasopressins

Topics: Animals; Blood Pressure; Desoxycorticosterone Acetate; Disease Models, Animal; Hypertension; Hypothalamus; Male; Membrane Potentials; Mice, Knockout; Neurons; Proton-Translocating ATPases; Rats, Wistar; Reaction Time; Receptors, Cell Surface; Renin; Renin-Angiotensin System; Shaw Potassium Channels; Sodium Chloride, Dietary; Time Factors; Up-Regulation; Vasopressins

Polycystic kidney disease (PKD) is a group of monogenetic conditions characterised by the progressive accumulation of multiple renal cysts and hypertension. One of the earliest features of PKD is a reduction in urinary concentrating capacity that impairs extracellular fluid conservation. Urinary concentrating impairment predisposes PKD patients to periods of hypohydration when fluid loss is not adequately compensated by fluid intake. The hypohydrated state provides a blood hyperosmotic stimulus for vasopressin release to minimise further water loss. However, over-activation of renal V2 receptors contributes to cyst expansion. Although suppressing vasopressin release with high water intake has been shown to impair disease progression in rodent models, whether this approach is efficacious in patients remains uncertain. The neural osmoregulatory pathway that controls vasopressin secretion also exerts a stimulatory action on vasomotor sympathetic activity and blood pressure during dehydration. Recurrent dehydration leads to a worsening of hypertension in rodents and cross-sectional data suggests that reduced urinary concentrating ability may contribute to hypertension development in the clinical PKD population. Experimental studies are required to evaluate this hypothesis and to determine the underlying mechanism.

Topics: Animals; Disease Progression; Drinking; Humans; Hypertension; Osmoregulation; Polycystic Kidney Diseases; Receptors, Vasopressin; Urine; Vasopressins

All three epithelial Na

Topics: Animals; Epithelial Sodium Channels; Hypertension; Hypothalamus; Kidney; Male; Osmolar Concentration; Rats, Inbred Dahl; Rats, Sprague-Dawley; Receptors, Mineralocorticoid; Sodium Chloride, Dietary; Supraoptic Nucleus; Vasopressins

Topics: Aldosterone; Blood Pressure; Humans; Hypertension; Osmolar Concentration; Sodium Chloride, Dietary; Vasopressins; Water

Several studies have suggested negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies have shown protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male spontaneously hypertensive rats (SHRs) maintained on water (SHR-Water) and SHRs drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto (WKY) rats were used as normotensive controls to discriminate between age-dependent and hypertension-dependent changes. Telemetry measurements of blood pressure were performed in rats between the 7th and 16th weeks of life. Anesthetized rats underwent echocardiographic, electrocardiographic, and direct left ventricular end-diastolic pressure (LVEDP) measurements. Hematoxylin and eosin as well as van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in the SHR-Water group compared with the WKY group (~20%). TMAO treatment increased plasma TMAO by four- to fivefold and did not affect the development of hypertension in SHRs. Sixteen-week-old rats in the SHR-Water and SHR-TMAO groups (12-wk TMAO treatment) showed similar blood pressures, angiopathy, and cardiac hypertrophy. However, the SHR-TMAO group had lower plasma NH

Topics: Animals; Antihypertensive Agents; Blood Pressure; Fibrosis; Hypertension; Male; Methylamines; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Rats, Wistar; Vasopressins

Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion and fibrosis, frequently leading to end-stage renal disease. Increased vasopressin and cAMP signaling, dysregulated calcium homeostasis, and hypertension play major roles in PKD progression. The guanylyl cyclase A agonist, B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti-hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on PKD progression in a rat model of PKD. Sustained BNP production significantly reduced kidney weight, renal cystic indexes and fibrosis, in concert with suppressed hepatic cystogenesis in vivo. In vitro, BNP decreased cystic epithelial cell proliferation, suppressed fibrotic gene expression, and increased intracellular calcium. Together, our data demonstrate multifaceted effects of sustained activation of guanylyl cyclase A on polycystic kidney and liver disease. Thus, targeting the guanylyl cyclase A-cGMP axis may provide a novel therapeutic strategy for hepatorenal fibrocystic diseases.

Topics: Animals; Cell Proliferation; Cyclic AMP; Cyclic GMP; Cysts; Disease Models, Animal; Disease Progression; Epithelial Cells; Female; Fibrosis; Genetic Vectors; Humans; Hypertension; Kidney; Liver; Liver Diseases; Male; Natriuretic Peptide, Brain; Parvovirinae; Polycystic Kidney, Autosomal Recessive; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Signal Transduction; Vasopressins

The orexin system is involved in arginine vasopressin (AVP) regulation, and its overactivation has been implicated in hypertension. However, its role in salt-sensitive hypertension (SSHTN) is unknown. Here, we tested the hypothesis that hyperactivity of the orexin system in the paraventricular nucleus (PVN) contributes to SSHTN via enhancing AVP signaling. Eight-week-old male Dahl salt-sensitive (Dahl S) and age- and sex-matched Sprague-Dawley (SD) rats were placed on a high-salt (HS; 8% NaCl) or normal-salt (NS; 0.4% NaCl) diet for 4 wk. HS intake did not alter mean arterial pressure (MAP), PVN mRNA levels of orexin receptor 1 (OX1R), or OX2R but slightly increased PVN AVP mRNA expression in SD rats. HS diet induced significant increases in MAP and PVN mRNA levels of OX1R, OX2R, and AVP in Dahl S rats. Intracerebroventricular infusion of orexin A (0.2 nmol) dramatically increased AVP mRNA levels and immunoreactivity in the PVN of SD rats. Incubation of cultured hypothalamus neurons from newborn SD rats with orexin A increased AVP mRNA expression, which was attenuated by OX1R blockade. In addition, increased cerebrospinal fluid Na

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Cells, Cultured; Disease Models, Animal; Hypertension; Male; Microinjections; Neurons; Orexin Receptors; Paraventricular Hypothalamic Nucleus; Phenylurea Compounds; Rats, Inbred Dahl; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Up-Regulation; Vasopressins

In industrialized countries, a large part of the population is daily exposed to low K(+) intake, a situation correlated with the development of salt-sensitive hypertension. Among many processes, adaptation to K(+)-restriction involves the stimulation of H,K-ATPase type 2 (HKA2) in the kidney and colon and, in this study, we have investigated whether HKA2 also contributes to the determination of blood pressure (BP). By using wild-type (WT) and HKA2-null mice (HKA2 KO), we showed that after 4 days of K(+) restriction, WT remain normokalemic and normotensive (112 ± 3 mmHg) whereas HKA2 KO mice exhibit hypokalemia and hypotension (104 ± 2 mmHg). The decrease of BP in HKA2 KO is due to the absence of NaCl-cotransporter (NCC) stimulation, leading to renal loss of salt and decreased extracellular volume (by 20 %). These effects are likely related to the renal resistance to vasopressin observed in HKA2 KO that may be explained, in part by the increased production of prostaglandin E2 (PGE2). In WT, the stimulation of NCC induced by K(+)-restriction is responsible for the elevation in BP when salt intake increases, an effect blunted in HKA2-null mice. The presence of an activated HKA2 is therefore required to limit the decrease in plasma [K(+)] but also contributes to the development of salt-sensitive hypertension.

Topics: Animals; Blood Pressure; Dinoprostone; H(+)-K(+)-Exchanging ATPase; Hypertension; Kidney; Mice; Mice, Inbred C57BL; Potassium; Potassium Deficiency; Solute Carrier Family 12, Member 3; Vasopressins

The participation of vasopressin in the mechanisms of resistant hypertension is unclear. We compared plasma copeptin concentration, a surrogate marker for vasopressin secretion, between patients with resistant hypertension and those with controlled blood pressure (CBP), in a post hoc analysis of the Prise en charge de l'Hypertension Artérielle RESistante au traitement trial.. After 4-week treatment with irbesartan 300 mg/day, hydrochlorothiazide 12.5 mg/day, and amlodipine 5 mg/day (baseline), 166 patients were classified as having resistant hypertension (n = 140) or CBP (n = 26) by ambulatory BP monitoring. Patients with resistant hypertension were then randomized for 12 weeks of sequential nephron blockade (n = 74) or sequential renin-angiotensin system blockade (n = 66). Plasma copeptin concentration was measured at baseline and week 12 by immunoassay.. Baseline plasma copeptin concentration was positively associated with male sex, plasma osmolality, BP, and negatively with glomerular filtration rate. It was higher in the resistant hypertension than in the CBP group [geometric mean 5.7 (confidence interval 95% 5.1-6.4) vs. 2.9 (2.3-3.9) fmol/ml, adjusted P < 0.0001). The relationship between plasma copeptin concentration and urinary osmolality was similar in the two groups. At 12 weeks, plasma copeptin concentration in patients whose BP was controlled by sequential nephron blockade or sequential renin-angiotensin system blockade [6.8 (5.6-8.2) and 4.3 (3.0-5.9) fmol/ml, respectively) remained significantly higher than in patients with CBP at baseline (P < 0.0001 vs. both).. In patients with resistant hypertension, plasma copeptin concentrations were approximately two-fold higher than those of patients with CBP, after adjustment for plasma osmolality. This difference was not accounted for by renal resistance to vasopressin, suggesting a primary reset of osmostat.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Biomarkers; Biphenyl Compounds; Blood Pressure; Coronary Vasospasm; Diuretics; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Hydrochlorothiazide; Hypertension; Irbesartan; Male; Middle Aged; Nephrons; Osmolar Concentration; Renin-Angiotensin System; Sex Factors; Tetrazoles; Vasopressins

Hyponatraemia is a common, potentially life-threatening, complication of thiazide diuretics. The mechanism of thiazide-induced hyponatraemia is incompletely understood. Previous experiments have suggested a direct effect of thiazide diuretics on the plasma membrane expression of aquaporin (AQP)2.. We examined the effects of a single re-exposure to hydrochlorothiazide (HCTZ) 50 mg on water balance, renal sodium handling and osmoregulation in 15 elderly hypertensive patients with a history of thiazide-induced hyponatraemia and 15 matched hypertensive controls using thiazide diuretics without previous hyponatraemia.. Patients with thiazide-induced hyponatraemia had significantly lower body weight and lower plasma sodium and osmolality at baseline. After HCTZ administration, plasma sodium and osmolality significantly decreased and remained lower in patients compared with controls (P < 0.001). Plasma antidiuretic hormone (ADH) and urine AQP2 were low or suppressed in patients, whereas solute and electrolyte-free water clearance was significantly increased compared with controls. Ad libitum water intake was significantly higher in patients (2543 ± 925 ml) than in controls (1828 ± 624 ml, P < 0.05), whereas urinary sodium excretion did not differ. In contrast, urea excretion remained significantly lower in patients (263 ± 69 mmol per 24 h) compared with controls (333 ± 97 mmol per 24 h, P < 0.05) and predicted the decrease in plasma sodium following HCTZ administration.. Thiazide diuretics are associated with markedly impaired free water excretion at low ADH and AQP2 in elderly patients. The higher water intake and lower urea excretion in patients points to an important role for polydipsia and urea-mediated water excretion in the pathogenesis of thiazide-induced hyponatraemia.

Topics: Aged; Aged, 80 and over; Aquaporin 2; Drinking; Electrolytes; Female; Humans; Hydrochlorothiazide; Hypertension; Hyponatremia; Kidney; Male; Middle Aged; Osmolar Concentration; Sodium; Sodium Chloride Symporter Inhibitors; Urea; Vasopressins; Water-Electrolyte Balance

The mechanisms by which dietary salt promotes hypertension are unknown. Previous work established that plasma [Na(+)] and osmolality rise in proportion with salt intake and thus promote release of vasopressin (VP) from the neurohypophysis. Although high levels of circulating VP can increase blood pressure, this effect is normally prevented by a potent GABAergic inhibition of VP neurons by aortic baroreceptors. Here we show that chronic high salt intake impairs baroreceptor inhibition of rat VP neurons through a brain-derived neurotrophic factor (BDNF)-dependent activation of TrkB receptors and downregulation of KCC2 expression, which prevents inhibitory GABAergic signaling. We show that high salt intake increases the spontaneous firing rate of VP neurons in vivo and that circulating VP contributes significantly to the elevation of arterial pressure under these conditions. These results provide the first demonstration that dietary salt can affect blood pressure through neurotrophin-induced plasticity in a central homeostatic circuit.

Topics: Animals; Baroreflex; Blood Pressure; Brain-Derived Neurotrophic Factor; Down-Regulation; Hypertension; K Cl- Cotransporters; Male; Neurons; Organ Culture Techniques; Rats; Rats, Long-Evans; Sodium Chloride, Dietary; Symporters; Vasopressins

Hemodynamic augmentation is utilized as a treatment in the setting of symptomatic cerebral vasospasm. This approach includes the use of vasopressors to induce hypertension with the aim of improved cerebral blood flow. Agents with potent alpha-1 antagonism properties, including clozapine, can inhibit or blunt the response of several vasopressor agents.. Case report.. A 54-year-old schizophrenic male with an aneurysmal subarachnoid hemorrhage required hemodynamic augmentation in which several vasopressor trials resulted in no or poor response. The addition of epinephrine resulted in a decrease of mean arterial pressure. Vasopressin initiation demonstrated an immediate vasopressor effect.. Vasopressors are an important treatment modality in symptomatic cerebral vasospasm. This case highlights the potential for clozapine to blunt the effects of vasopressors; or in the case of epinephrine, it causes a reversal effect. Vasopressin may be considered an agent of choice in patients who have recently taken clozapine and require hemodynamic augmentation.

Topics: Clozapine; Drug Interactions; Epinephrine; GABA Antagonists; Humans; Hypertension; Intracranial Aneurysm; Male; Middle Aged; Schizophrenia; Subarachnoid Hemorrhage; Vasoconstrictor Agents; Vasopressins; Vasospasm, Intracranial

Vasopressin secretion from the posterior pituitary gland is determined by action potential discharge of hypothalamic magnocellular neurosecretory cells. Vasopressin is a potent vasoconstrictor, but vasopressin levels are paradoxically elevated in some patients with established hypertension. To determine whether vasopressin neurons are excited in hypertension, extracellular single-unit recordings of vasopressin neurons from urethane-anaesthetized Cyp1a1-Ren2 rats with inducible angiotensin-dependent hypertension were made. The basal firing rate of vasopressin neurons was higher in hypertensive Cyp1a1-Ren2 rats than in non-hypertensive Cyp1a1-Ren2 rats. The increase in firing rate was specific to vasopressin neurons because oxytocin neuron firing rate was unaffected by the induction of hypertension. Intravenous injection of the α1-adrenoreceptor agonist, phenylephrine (2.5 μg/kg), transiently increased mean arterial blood pressure to cause a baroreflex-induced inhibition of heart rate and vasopressin neuron firing rate (by 52 ± 9%) in non-hypertensive rats. By contrast, intravenous phenylephrine did not inhibit vasopressin neurons in hypertensive rats, despite a similar increase in mean arterial blood pressure and inhibition of heart rate. Circulating angiotensin II can excite vasopressin neurons via activation of afferent inputs from the subfornical organ. However, the increase in vasopressin neuron firing rate and the loss of inhibition by intravenous phenylephrine were not blocked by intra-subfornical organ infusion of the angiotensin AT1 receptor antagonist, losartan. It can be concluded that increased vasopressin neuron activity at the onset of hypertension is driven, at least in part, by reduced baroreflex inhibition of vasopressin neurons and that this might exacerbate the increase in blood pressure at the onset of hypertension.

Topics: Adrenergic alpha-1 Receptor Agonists; Angiotensin II Type 1 Receptor Blockers; Animals; Baroreflex; Blood Pressure; Hypertension; Losartan; Male; Neurons; Phenylephrine; Pituitary Gland; Rats; Rats, Inbred F344; Rats, Transgenic; Subfornical Organ; Vasopressins

The abnormal blood volume regulation is one of the most important pathogenesis in postural tachycardia syndrome in children. This study was designed to investigate the plasma atrial natriuretic peptide and antidiuretic hormone levels in postural tachycardia syndrome children, and their associations with the changes in heart rate and blood pressure in head-up test.. Twenty-one postural tachycardia syndrome patients ((12 ± 2) years) and 26 healthy children ((12 ± 1) years) were included. According to blood pressure changes in head-up test, the postural tachycardia syndrome patients were divided into two subgroups: postural tachycardia syndrome with orthostatic hypertension and postural tachycardia syndrome without orthostatic hypertension. The plasma atrial natriuretic peptide and antidiuretic hormone levels were measured using enzyme-linked immunosorbent assay.. The plasma atrial natriuretic peptide level in postural tachycardia syndrome patients was higher than the control (P = 0.004), whereas the difference in plasma antidiuretic hormone level between postural tachycardia syndrome and controls was not significant (P = 0.222). The plasma antidiuretic hormone level of patients suffering from postural tachycardia syndrome with orthostatic hypertension was much higher than that of children having postural tachycardia syndrome without orthostatic hypertension (P < 0.05). In postural tachycardia syndrome patients, the upright max heart rate was positively correlated with the plasma atrial natriuretic peptide level (r = 0.490, P < 0.05) and the upright systolic blood pressure was positively correlated with the plasma antidiuretic hormone levels (r = 0.472, P < 0.05).. There was a disturbance of plasma atrial natriuretic peptide and antidiuretic hormone in postural tachycardia syndrome children.

Topics: Adolescent; Atrial Natriuretic Factor; Case-Control Studies; Child; Humans; Hypertension; Postural Orthostatic Tachycardia Syndrome; Vasopressins

Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

Topics: Adult; Animals; Arginine Vasopressin; Biomarkers; Blood Pressure; Disease Models, Animal; Early Diagnosis; Endothelium, Vascular; Female; Glycopeptides; Humans; Hypertension; Kidney Glomerulus; Male; Mice; Mice, Inbred C57BL; Pre-Eclampsia; Pregnancy; Proteinuria; ROC Curve; Time Factors; Vasopressins

NADPH oxidase-generated reactive oxygen species (ROS) are highly implicated in the development of angiotensin II (AngII)-dependent hypertension mediated in part through the hypothalamic paraventricular nucleus (PVN). This region contains vasopressin and non-vasopressin neurons that are responsive to cardiovascular dysregulation, but it is not known whether ROS is generated by one or both cell types in response to "slow-pressor" infusion of AngII. We addressed this question using ROS imaging and electron microscopic dual labeling for vasopressin and p47(phox), a cytoplasmic NADPH oxidase subunit requiring mobilization to membranes for the initiation of ROS production. C57BL/6 mice or vasopressin-enhanced green fluorescent protein (VP-eGFP) mice were infused systemically with saline or AngII (600 ng · kg(-1) · min(-1), s.c.) for 2 weeks, during which they slowly developed hypertension. Ultrastructural analysis of the PVN demonstrated p47(phox) immunolabeling in many glial and neuronal profiles, most of which were postsynaptic dendrites. Compared with saline, AngII recipient mice had a significant increase in p47(phox) immunolabeling on endomembranes just beneath the plasmalemmal surface (+42.1 ± 11.3%; p < 0.05) in non-vasopressin dendrites. In contrast, AngII infusion decreased p47(phox) immunolabeling on the plasma membrane (-35.5 ± 16.5%; p < 0.05) in vasopressin dendrites. Isolated non-VP-eGFP neurons from the PVN of AngII-infused mice also showed an increase in baseline ROS production not seen in VP-eGFP neurons. Our results suggest that chronic low-dose AngII may offset the homeostatic control of blood pressure by differentially affecting membrane assembly of NADPH oxidase and ROS production in vasopressin and non-vasopressin neurons located within the PVN.

Topics: Angiotensin II; Animals; Cell Membrane; Dendrites; Drug Administration Schedule; Drug Delivery Systems; Excitatory Amino Acid Agonists; Green Fluorescent Proteins; HEK293 Cells; Humans; Hypertension; In Vitro Techniques; Intracellular Membranes; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Immunoelectron; N-Methylaspartate; NADPH Oxidases; Neuroglia; Neurons; Paraventricular Hypothalamic Nucleus; Protein Transport; Reactive Oxygen Species; Transfection; Vasoconstrictor Agents; Vasopressins

It is well recognized that vasopressin modulates the neurogenic control of the circulation. Here, we report the central mechanisms by which vasopressin modulates cardiovascular response to stress induced by immobilization.. Experiments were performed in conscious male Wistar rats equipped with radiotelemetric device for continuous measurement of haemodynamic parameters: systolic and diastolic BP and heart rate (HR). The functioning of the spontaneous baro-receptor reflex (BRR) was evaluated using the sequence method and the following parameters were evaluated: BRR sensitivity (BRS) and BRR effectiveness index (BEI).. Under baseline physiological conditions intracerebroventricular injection of 100 and 500 ng of selective non-peptide V1a or V1b or V2 receptor antagonist did not modify BP, HR and BRR. Rats exposed to 15 min long stress by immobilization exhibited increase of BP, HR, reduction of BRS and no change in BEI. Pretreatment of rats with V1a receptor antagonist did not modulate the BP, HR, BRS and BEI response to stress. Pretreatment of rats with V1b receptor and V2 receptor antagonist, at both doses, prevented BRR desensitization and tachycardia, but failed to modulate stress-induced hypertension.. Vasopressin by the stimulation of central V1b- and V2-like receptors mediates stress-induced tachycardia and BRR desensitization. If these mechanisms are involved, BRR desensitization in heart failure and hypertension associated with poor outcome, they could be considered as novel targets for cardiovascular drug development.

Topics: Allostasis; Animals; Anti-Anxiety Agents; Antidiuretic Hormone Receptor Antagonists; Baroreflex; Cerebral Ventricles; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension; Injections, Intraventricular; Male; Nerve Tissue Proteins; Neurons; Pilot Projects; Random Allocation; Rats; Rats, Wistar; Receptors, Vasopressin; Restraint, Physical; Stress, Physiological; Stress, Psychological; Tachycardia; Vasopressins

An indispensable role for the brain renin-angiotensin system (RAS) has been documented in most experimental animal models of hypertension. To identify the specific efferent pathway activated by the brain RAS that mediates hypertension, we examined the hypothesis that elevated arginine vasopressin (AVP) release is necessary for hypertension in a double-transgenic model of brain-specific RAS hyperactivity (the "sRA" mouse model). sRA mice experience elevated brain RAS activity due to human angiotensinogen expression plus neuron-specific human renin expression. Total daily loss of the 4-kDa AVP prosegment (copeptin) into urine was grossly elevated (≥8-fold). Immunohistochemical staining for AVP was increased in the supraoptic nucleus of sRA mice (~2-fold), but no quantitative difference in the paraventricular nucleus was observed. Chronic subcutaneous infusion of a nonselective AVP receptor antagonist conivaptan (YM-087, Vaprisol, 22 ng/h) or the V(2)-selective antagonist tolvaptan (OPC-41061, 22 ng/h) resulted in normalization of the baseline (~15 mmHg) hypertension in sRA mice. Abdominal aortas and second-order mesenteric arteries displayed AVP-specific desensitization, with minor or no changes in responses to phenylephrine and endothelin-1. Mesenteric arteries exhibited substantial reductions in V(1A) receptor mRNA, but no significant changes in V(2) receptor expression in kidney were observed. Chronic tolvaptan infusion also normalized the (5 mmol/l) hyponatremia of sRA mice. Together, these data support a major role for vasopressin in the hypertension of mice with brain-specific hyperactivity of the RAS and suggest a primary role of V(2) receptors.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Blood Pressure; Brain; Gene Expression; Hypertension; Hypothalamus; Mice; Mice, Transgenic; Receptors, Vasopressin; Renin-Angiotensin System; Tolvaptan; Vasopressins

Topics: Animals; Blood Pressure; Brain; Hypertension; Renin-Angiotensin System; Vasopressins

Hypertension is a common chronic condition in many patients requiring anesthesia. Pharmacologic therapy is a mainstay of treatment for hypertension, with angiotensin-converting enzyme (ACE) inhibitors being a frequently prescribed class of drugs. The American College of Cardiology and American Heart Association 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery provide information on many drug classes used in the treatment of hypertension; noticeably absent is a guideline for ACE inhibitors. Literature demonstrates that practice standards vary on whether ACE inhibitor regimens are continued or withheld during the preoperative period. When ACE inhibitor therapy is continued in patients undergoing general anesthesia, varying degrees of hypotension can be seen depending on confounding patient variables and the type of surgical procedure. In some instances, this hypotension can be refractory to traditional interventions such as administration of a fluid bolus, ephedrine, or phenylephrine. Vasopressin and methylene blue have been found to be effective treatments for ACE inhibitor-associated refractory hypotension. With the prevalence of hypertension and use of ACE inhibitors, anesthesia providers are likely to encounter refractory hypotension of this nature. The absence of guidelines regarding ACE inhibitors in the perioperative period contributes to a lack of consistency in practice.

Topics: Angiotensin-Converting Enzyme Inhibitors; Education, Continuing; Enzyme Inhibitors; Humans; Hypertension; Hypotension; Methylene Blue; Nurse Anesthetists; Perioperative Period; Vasoconstrictor Agents; Vasopressins

The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor, and vasopressin mRNA levels. Plasma vasopressin levels were determined by ELISA. Double-transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor short-hairpin RNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared with the control virus treatment in double-transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double-transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease in sympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with downregulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice.

Topics: Angiotensin II; Angiotensinogen; Animals; Baroreflex; Blood Pressure; Blotting, Western; Brain; Cell Line, Tumor; Humans; Hypertension; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Prorenin Receptor; Receptor, Angiotensin, Type 1; Receptors, Cell Surface; Renin; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Vasopressins

The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension. Also, AVP has vasoconstrictor, mitogenic, hyperplasic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Furthermore, cholesterol blood levels are also associated with hypertension, although the underlying mechanism is not known. Here we analyze the relationship between blood total cholesterol levels and serum vasopressin- degrading cystyl-aminopeptidase activity (AVP-DA) in healthy humans, and the differences between men and women. Linear correlation coefficients were calculated to test relationships between AVP-DA and blood total cholesterol levels. Sex differences were observed for AVP-DA, being this activity higher in men than in women. According to the linear model of the regression analysis, AVP-DA showed a significant negative correlation with blood total cholesterol levels in men, whereas no correlation was observed in women. Several studies in humans demonstrate the existence of greater plasma AVP concentrations in normal men compared to normal women, which could explain the gender-differences observed in the present work in relation with AVP-DA. However, AVP-DA is related to blood cholesterol levels only in men, although in our hands, women showed higher blood cholesterol levels than men. This could indicate that the risk of high cholesterol-related hypertension is more probable in men than in women. Although AVP-DA misregulation could be involved in the pathogenesis of hypertension, its relation with cholesterol levels appears only in men, but not in women.

Topics: Adult; Aged; Cholesterol; Female; Hemostatics; Humans; Hypertension; Linear Models; Male; Middle Aged; Sex Factors; Vasopressins

Vasopressin (VP)-, neuropeptide FF (NPFF)-, and tyrosine hydroxylase (TH)-expressing neurons were studied by means of single and double immunocytochemistry in the human brainstem of controls who died suddenly due to trauma and of patients who suffered from essential hypertension and died due to acute myocardial infarction, while in one case there was brain hemorrhage. In the control and hypertensive groups VP fibers and NPFF neurons and fibers were the most abundantly present in the dorsal vagal complex, especially in the dorsal motor nucleus of the vagus. Numerous VP and NPFF fibers formed synaptic-like contacts with neuronal profiles in the dorsointermediate, centrointermediate, ventrointermediate, caudointermediate, and caudal parts of the dorsal motor nucleus of vagus as well as adjacent medial and intermediate subnuclei of the solitary nucleus. VP, but not NPFF, positive fibers were found to vastly contact TH-positive neuronal profiles in A2/C2, A2, and ambiguus nucleus (Amb). The density of VP fibers in the dorsal motor nucleus of the vagus and Amb did not differ between hypertensive patients and controls, whereas the density of NPFF fibers in hypertensives was 3.19 times lower in the dorsal motor nucleus of vagus and markedly decreased in the Amb. In both groups, VP and NPFF were scarcely present in the pain pathways, suggesting that these peptides are not crucially involved in nociceptive control in human. The reduction of NPFF release within the dorsal motor nucleus and Amb could serve as a possible cause of the impairment of cardiac vagal control in hypertensive patients.

Topics: Adult; Aged; Brain Stem; Female; Humans; Hypertension; Immunohistochemistry; Male; Middle Aged; Neurons; Neuropeptides; Vasopressins

A co-morbidity of sleep-disordered breathing is hypertension associated with elevated sympathetic nerve activity, which may result from chronic intermittent hypoxia (CIH). CIH evokes plasticity in cardiorespiratory regulating sites, including the paraventricular nucleus (PVN), which acts to sustain increased sympathetic nerve activity. Our working hypothesis is that vasopressin neurons mediate the sustained increase in blood pressure and altered breathing associated with CIH. In a series of neuroanatomical experiments, we determined if vasopressin-containing PVN neurons innervate rostral ventrolateral medulla (RVLM), and altered cardiorespiratory responses induced by CIH conditioning (8h/day for 10 days) is mediated by vasopressin-V(1A ) receptor signaling in the medulla. In the first set of experiments, cholera toxin β subunit was microinjected into the RVLM to delineate innervation of the PVN. Immunohistochemistry data showed vasopressin-containing PVN neurons were double-labeled with cholera toxin β subunit, indicating vasopressin projection to the RVLM. In the second set, sections of the medulla were immunolabeled for vasopressin V(1A ) receptor, and its expression was significantly higher in the RVLM and in the neighboring rostral ventral respiratory column in CIH- than from RA-conditioned rats. In a series of physiological experiments,we determined if blocking the vasopressin V(1A )receptor in the medulla would normalize blood pressure in CIH-conditioned rats and also attenuate the evoked responses to PVN disinhibition.Blood pressure, heart rate, diaphragmatic and genioglossus muscle activity were recorded in anesthetized, ventilated and vagotomized rats. The PVN was disinhibited by microinjecting bicuculline before and after blocking vasopressin V(1A ) receptors in the RVLM/rostral ventral respiratory column. In RA-conditioned rats, PVN disinhibition increased blood pressure, heart rate, minute diaphragmatic and genioglossus muscle activity, and these increases were attenuated after blocking the vasopressin V(1A ) receptor. In CIH-conditioned rats, a significantly greater dose of blocker was required to blunt these physiological responses and it also normalized the baseline blood pressure. Our findings indicate that vasopressin is the neuropeptide released from PVN neurons that modulates cardiorespiratory output via the RVLM and rostral ventral respiratory column.

Topics: Animals; Bicuculline; Blood Pressure; Chronic Disease; Diaphragm; GABA-A Receptor Antagonists; Heart Rate; Hypertension; Hypoxia; Medulla Oblongata; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Signal Transduction; Sleep Apnea Syndromes; Vasopressins

The dysregulation of arginine vasopressin (AVP) release and activation of vasopressin V(1A) and V(2) receptors may play a role in disease. The in vitro and in vivo pharmacology of RWJ-676070, a potent, balanced antagonist of both the V(1A) and V(2) receptors is described. RWJ-676070 binding and intracellular functional antagonist activity was characterized using cells expressing V(1A), V(1B) or V(2) receptors. Its inhibition of V(1A) receptor-mediated contraction of vascular rings and platelet aggregation was determined. V(2) receptor-medated aquaresis was determined in rats, dogs and monkeys. V(1A) receptor-mediated inhibitory activity was assessed in vivo in a vasopressin-induced hypertension model and in normotensive rats and in two hypertensive rat models. RWJ-676070 inhibited AVP binding to human V(1A) and V(2) receptors (Ki=1 and 14 nM, respectively). RWJ-676070 inhibited V(1A) receptor-induced intracellular calcium mobilization and V(2) receptor-induced cAMP accumulation with Ki values of 14 nM and 13 nM, respectively. The compound was slightly less potent against rat V(1A) receptors. RWJ-676070 inhibited V(1A) receptor-mediated vasoconstriction in rat and dog vascular rings and AVP-induced human platelet aggregation. Dose dependent aquaresis was demonstrated in rats, dogs and monkeys following oral administration. RWJ-676070 inhibited AVP-induced hypertension in rats but had no effect on arterial pressure in normotensive and spontaneously hypertensive rats but did decrease arterial pressure in Dahl, salt-sensitive hypertensive rats. RWJ-676070 is a new, potent antagonist of V(1A) and V(2) receptors that may be useful for treatment of diseases benefiting from balanced inhibition of both V(1A) and V(2) receptors.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Hypertension; In Vitro Techniques; Macaca fascicularis; Male; Platelet Aggregation; Rats; Rats, Inbred SHR; Spiro Compounds; Vasoconstriction; Vasopressins

The mechanisms involved in the development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clear. We hypothesized that OSA patients have an abnormal renal handling of sodium and water during the night.. We studied 29 OSA patients and 19 healthy controls at night with serial determinations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), aldosterone (Aldo), fractional urinary excretion of sodium (FE(Na)), free water clearance (C(H2O)), urinary excretion of aquaporin 2 (u-AQP2), systolic blood pressure (SBP), diastolic blood pressure (DBP) and oxygen saturation.. OSA patients had a higher FE(Na) (0.6 (0.4-1.0) versus 0.4 (0.3-0.6) %; p = 0.017), SBP (129 (114-145) versus 114 (106-122) mmHg; p = 0.001) and DBP (81 (72-87) versus 71 (65-74) mmHg; p<0.001) than healthy controls at night. In hypertensive OSA patients, the FE(Na) correlated significantly with the change in nocturnal DBP (r (2) = 0.411; p = 0.010). Mean level of AVP during the night was higher in OSA patients compared with healthy controls (1.1 (0.8-1.4) versus 0.8 (0.6-1.1) pmol/L; p = 0.033) and correlated with SBP. ANP, BNP, Aldo, C(H2O) and u-AQP2 were the same in OSA and controls.. We conclude that the higher fractional excretion of sodium in OSA is most likely attributable to pressure natriuresis. The correlation between mean AVP and blood pressure suggests that AVP may be part of the pathogenetic mechanism underlying hypertension in these patients.

Topics: Adult; Age Factors; Aldosterone; Aquaporin 2; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hypertension; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Oxygen; Potassium; Sex Factors; Sleep Apnea, Obstructive; Sodium; Vasopressins; Water

The Vav family is a group of signal transduction molecules that activate Rho/Rac GTPases during cell signaling. Experiments using knockout mice have indicated that the three Vav proteins present in mammals (Vav1, Vav2, and Vav3) are essential for proper signaling responses in hematopoietic cells. However, Vav2 and Vav3 are also highly expressed in nonhematopoietic tissues, suggesting that they may have additional functions outside blood cells. Here, we report that this is the case for Vav2, because the disruption of its locus in mice causes tachycardia, hypertension, and defects in the heart, arterial walls, and kidneys. We also provide physiological and pharmacological evidence demonstrating that the hypertensive condition of Vav2-deficient mice is due to a chronic stimulation of the renin/angiotensin II and sympathetic nervous systems. Together, these results indicate that Vav2 plays crucial roles in the maintenance of cardiovascular homeostasis in mice.

Topics: Adrenal Glands; Aldosterone; Animals; Aorta; Endothelins; Gene Expression Regulation; Guanine Nucleotide Exchange Factors; Heart Ventricles; Hypertension; Kidney; Kidney Function Tests; Mice; Mice, Knockout; Phenotype; Proto-Oncogene Proteins c-vav; Renin-Angiotensin System; Sympathetic Nervous System; Tachycardia; Vasopressins

Adult patients with hypopituitarism are treated by the replacement of deficient hormones, although GH has not been substituted until March 2006 in Japan except for clinical trial. This study examines which hormonal status influences the prevalence of vascular risk disorders in hypopituitary adults. A sample of 263 adult patients with hypopituitarism was studied, among whom there were various hormonal status such as no deficiency, treated or untreated deficiency of each pituitary hormone. Analysis of adult patients with hypopituitarism showed that hypertension was more prevalent in the older than in younger patients and in male than in female patients. Hypercholesterolemia and hypertriglyceridemia were more prevalent in patients with TSH deficiency even with thyroxine substitution than those without TSH deficiency. Both obesity and hypertension were less prevalent in patients with treated ACTH deficiency than those without ACTH deficiency. Obesity was more prevalent in patients with treated vasopressin deficiency than those without vasopressin deficiency. These results provide evidence that glucocorticoid substitution in ACTH deficient adults was favorable to prevent obesity and hypertension but that the thyroxine substitution in TSH deficient adults appeared rather insufficient to prevent hyperlipidemia.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Age Distribution; Aged; Aged, 80 and over; Female; Hormone Replacement Therapy; Humans; Hypercholesterolemia; Hypertension; Hypertriglyceridemia; Hypopituitarism; Male; Middle Aged; Obesity; Prevalence; Risk Factors; Sex Distribution; Thyrotropin; Thyroxine; Vascular Diseases; Vasopressins

Dialysis hypertension is a complex disorder in which ambient vascular resistance is too high for the blood volume. van der Zee et al. remind us that this is contingent upon the endothelium itself, and that endothelial dysfunction is integral to uremia. Thus, while vasopressin may not abolish dialysis hypotension, its effects highlight the influence of uremia on the autocrine and neuroendocrine control of cardiovascular physiology.

Topics: Humans; Hypertension; Renal Dialysis; Vasopressins

The anticoronaryspastic and antibronchospastic activities of ethanolic and aqueous extracts of Valeriana officinalis L. roots were investigated in anaesthetized guinea-pigs and the results were correlated with the qualitative/quantitative chemical composition of the extracts in order to account for some of the common uses of this plant. The protective effects of orally administered ethanolic and aqueous extracts (50, 100 and 200 mg/kg) were evaluated against pitressin-induced coronary spasm and pressor response in guinea-pigs and were compared with those of nifedipine. Furthermore, the protective effects against histamine-induced and Oleaceae antigen challenge-induced bronchospasm were evaluated. Finally, the two valerian extracts were analytically characterized by qualitative and quantitative chromatographic analysis. The results showed that the two valeriana extracts possessed significant anticoronaryspastic, antihypertensive and antibronchospastic properties. These were similar to those exhibited by nifedipine and are due to the structural features of the active principles they contain. This study justifies the traditional use of this plant in the treatment of some respiratory and cardiovascular disorders.

Topics: Allergens; Animals; Antihypertensive Agents; Bronchial Spasm; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Coronary Vasospasm; Guinea Pigs; Histamine; Hypertension; Male; Oleaceae; Parasympatholytics; Plant Extracts; Plant Roots; Spectrophotometry, Ultraviolet; Ultrasonics; Valerian; Vasoconstrictor Agents; Vasopressins

Left ventricular (LV) hypertrophy is related to blood pressure level and neurohormonal factors. The authors previously demonstrated that arterial norepinephrine levels predict LV mass in middle-aged men who developed hypertension through 20 years. The aim of this 20-year prospective study was to investigate arterial vasopressin, aldosterone, and renin as long-term predictors of LV mass. Normotensives (n=17), subjects who developed hypertension (n=17), and sustained hypertensives (n=22) were compared at baseline (42 years) and at follow-up (62 years). There were no significant differences in baseline vasopressin, aldosterone, or renin levels. The group with sustained hypertension had more LV hypertrophy (P=.025) at follow-up. Among new hypertensives, multiple regression analysis demonstrated that baseline arterial vasopressin (beta-0.53; P=.041) and aldosterone (beta-0.56;P=.032) independently explained LV mass index (R(2)=0.85; P=.035). In conclusion, baseline arterial vasopressin and aldosterone, but not renin, appear to predict LV mass in middle-aged men who developed hypertension over a 20-year period.

Topics: Adult; Aldosterone; Analysis of Variance; Antihypertensive Agents; Arteries; Biomarkers; Blood Pressure; Cross-Sectional Studies; Echocardiography; Follow-Up Studies; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Pilot Projects; Predictive Value of Tests; Prospective Studies; Regression Analysis; Renin; Time Factors; Vasopressins

1. High-sodium intake may increase blood pressure and diabetes is a salt-sensitive condition. In the present study, we evaluated cardiovascular changes and their neurohumoral mechanisms in streptozotocin (STZ)-diabetic rats that underwent chronic salt loading. 2. We studied male Wistar rats (150-280 g) 14 days after the injection of either STZ (50 mg/kg, i.v.; D; n = 18) or citrate buffer (C; n = 16). After the induction of diabetes, animals were maintained for 14 days with free access to standard rat chow and tap water (C and D groups) or 1% NaCl solution (C-S and D-S groups). We conducted two experiments. Experiment 1 consisted of basal arterial pressure (AP) measurement (30 min) followed by the evaluation of AP responsiveness to phenylephrine and sodium nitroprusside. One day later, with the rats anaesthetized, a blood sample was collected to test for glycaemia, plasma angiotensin-converting enzyme (ACE) activity and renin. Kidneys were removed for the determination of tissue ACE activity. Experiment 2 comprised 24 h urine collection followed by 3 days of cardiovascular records, which consisted of a 30 min basal AP measurement, followed by injection of blockers of the vasopressin system, the renin-angiotensin system (RAS) and the sympathetic system. Basal haemodynamic data, baroreflex evaluation and AP responses to blockade of the vasopressin system with vasopressin V(1) receptor antagonist (aAVP; 10 mg/kg, i.v.), the RAS by losartan (10 mg/kg, i.v.) and the sympathetic system by hexamethonium (20 mg/kg, i.v.) were determined. 3. Glycaemia was similar between C and C-S (P = 0.612) and between D and D-S (P = 0.552), but higher in diabetic compared with non-diabetic rats (P < 0.0001). The D-S rats had an increment of 24% in mean AP compared with D (120 +/- 4 vs 97 +/- 2 mmHg, respectively; P = 0.0001), which was not seen in C-S compared with C rats. A positive association was noted between urinary sodium and mean AP (r = 0.37; P = 0.04). Plasma renin was undetectable in D-S rats. The response to acute drug blockade of vasopressin and the RAS was similar among groups, but hexamethonium elicited a more pronounced decrease in AP in D-S compared with D rats (P = 0.001). 4. The main neurohumoral mechanisms of salt-induced cardiovascular changes in STZ-diabetes are increased sodium and vascular sensitivity to adrenergic stimuli, which act in combination to produce a final result of higher AP levels, a finding not observed in control rats. Baroreflex derangemen

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Arginine Vasopressin; Baroreflex; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Ganglionic Blockers; Heart Rate; Hematocrit; Hexamethonium; Hormone Antagonists; Hypertension; Kidney; Losartan; Male; Nitroprusside; Organ Size; Peptidyl-Dipeptidase A; Phenylephrine; Rats; Rats, Wistar; Renin; Renin-Angiotensin System; Sodium Chloride, Dietary; Sympathetic Nervous System; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Topics: Humans; Hypertension; Urine; Vasopressins

It remains unclear whether the activation of kappa-opioid receptors has strong hypotensive effects under hypertensive condition, and the underlying mechanisms have not yet been investigated. Therefore, the present study is designed to use spontaneously hypertensive rats (SHR) to investigate the effects of a kappa-opioid receptor agonist on the regulation of urinary formation in hypertensive conditions and to identify its underlying mechanism.. The hemodynamics, urine flow rate, vasodilatation of isolated renal artery, and plasma hormones were determined by physiological in vivo experimental technique, isolated artery perfusion technique and radioimmunoassay.. Intravenous administration of U50, 448H significantly decreased mean arterial blood pressure in both Wistar-Kyoto (WKY) rats and SHR. However, the blood pressure vasodepressor effect of U50, 448H was much more profound in SHR than in WKY rats. Administration of U50, 448H in SHR not only caused significantly greater effects in increasing urine volume and decreasing plasma anti-diuretic hormone than in WKY rats, but also caused significant reduction in plasma angiotensin. Moreover, vasodilatory effect of U50, 488H was significantly exhibited in the renal artery segments isolated from SHR. All effects described above were abolished by nor-binaltorphimine.. These data indicate that the depressor effect of U50, 488H in SHR is significantly stronger than that in WKY rats, and the effect is mediated or modulated by a kappa-opioid receptor sensitive mechanism. The sensitized hypotensive effect of U50, 488H in SHR may be attributed, in part, to its vasodilatory effect, enhanced beneficial effect on plasma humoral factors, and stronger diuretic effect in these hypertensive animals.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Angiotensins; Animals; Antihypertensive Agents; Blood Pressure; Diuresis; Hypertension; In Vitro Techniques; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Opioid, kappa; Renal Artery; Urodynamics; Vasodilation; Vasopressins

This study investigates the plasma vasoactive substances and antioxidant enzymes levels in prehypertensive patients.. Patients were scruited according to JNC-7 and divided into three groups: 74 normotensive subjects (NT group, 38 males, mean age 47.15 +/- 7.77 years old); 51 prehypertensive patients (PH group, 29 males, mean age 47.82 +/- 5.16 years old) and 71 essential hypertensive patients (EH group, 37 males, mean age 48.25 +/- 7.97 years old). Serum lipids and plasma angiotensin II (Ang II), endothelin (ET), vasopressin (AVP), calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GPX) by radioimmunoassay and enzyme linked immunosorbent assay.. Serum Lipids (TG, CHO and LDL) were significantly higher in the PH and EH groups compared to NT group (all P < 0.05). Ang II, AVP and ET were significantly increased while CGRP decreased in the EH group than that in NT group (all P < 0.05). SOD was significantly lower while GPX significantly higher. Further more, in the PH and EH groups than those in the NT group (all P < 0.05).. SOD was reduced and GPX increased in prehypertensive patients.

Topics: Adult; Angiotensin II; Antioxidants; Blood Pressure; Calcitonin Gene-Related Peptide; Case-Control Studies; Endothelins; Female; Glutathione Peroxidase; Humans; Hypertension; Male; Middle Aged; Nitric Oxide Synthase; Plasma; Superoxide Dismutase; Vasopressins

A 52-year-old woman with hypertension and Graves' disease was scheduled for surgical removal of a meningioma. Intraoperative events were significant for hypotension requiring a vasopressin infusion. Prophylactic dolasetron was administered to the patient before emergence. The patient's trachea was easily extubated and she was neurologically intact at the end of the surgical procedure. On transport to the neurological intensive care unit, the patient developed torsades de pointes, requiring cardiopulmonary resuscitation, before a return to normal sinus rhythm.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Antiemetics; Cardiopulmonary Resuscitation; Electrocardiography; Female; Follow-Up Studies; Graves Disease; Humans; Hypertension; Hypotension; Indoles; Intraoperative Complications; Intubation, Intratracheal; Meningeal Neoplasms; Meningioma; Middle Aged; Postoperative Complications; Propanolamines; Quinolizines; Risk Factors; Torsades de Pointes; Vasoconstrictor Agents; Vasopressins

Aldosterone plays a crucial role in controlling mineral balance in our body. The mechanism of aldosterone has been reported to elevate renal Na+ reabsorption by stimulating expression of epithelial Na+ channel (ENaC) and also activate an ENaC-regulating protein kinase, serum and glucocorticoid-regulated kinase 1 (SGK1). However, it is unknown whether aldosterone shows its stimulatory action on ENaC and SGK1 under an abnormal, salt-sensitive hypertensive condition. To clarify this point, we studied how aldosterone regulates expression of ENaC and SGK1 in Dahl salt-sensitive (DS) rat that shows hypertension with high salt diet. RNA and protein were extracted from the kidney 6 h after application of aldosterone (1.5 mg/kg body weight) subcutaneously injected into adrenalectomized DS and Dahl salt-resistant (DR) rats. Aldosterone decreased mRNA expression of beta- and gamma-ENaC in DS rat unlike DR rat, while aldosterone increased alpha-ENaC mRNA expression in DS rat similar to DR rat. Further, we found that aldosterone elevated SGK1 expression in DR rat, but not in DS rat. These observations indicate that ENaC and SGK1 are abnormally regulated by aldosterone in salt-sensitive hypertensive rats, suggesting that disturbance of the aldosterone regulation would be one of factors causing salt-sensitive hypertension.

Topics: Aldosterone; Animals; Blotting, Western; Body Weight; Epithelial Sodium Channels; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Hypertension; Immediate-Early Proteins; Kidney; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Models, Statistical; Phosphorylation; Protein Serine-Threonine Kinases; Rats; Rats, Inbred Dahl; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Salts; Sodium; Sodium Channels; Time Factors; Vasopressins

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076-F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207-217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-beta-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, alpha- and gamma-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and gamma-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, alpha- or gamma-ENaC or increased MAP associated with "escape."

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Adrenalectomy; Aldosterone; Animals; Blood Pressure; Corticosterone; Deamino Arginine Vasopressin; Diuresis; Drinking; Epithelial Sodium Channels; Gene Expression Regulation; Glomerular Filtration Rate; Hyperaldosteronism; Hypertension; Kidney Tubules, Collecting; Male; Natriuresis; Rats; Rats, Sprague-Dawley; Sodium Channels; Sodium Chloride Symporters; Vasopressins

Androgens modulate vascular tone and hypertension development. Rho kinase contributes to norepinephrine- (NE) and vasopressin- (AVP) induced vasoconstriction. This study tested the hypothesis that Rho kinase contributes to androgen amplification of renal vasoconstrictor responses to NE or AVP in isolated perfused kidney of spontaneously hypertensive rats (SHRs).SHRs (5 weeks) underwent sham operation, castration, or castration with testosterone replacement. At 16-17 weeks, mean arterial pressure and heart rate were measured in conscious SHRs. Renal vascular reactivity to NE (10 to 10 mol) and to AVP (10 to 10 mol) was assessed in an isolated perfused kidney preparation before and after Rho kinase inhibitor treatment (fasudil; 15 microM). Castration reduced mean arterial pressure, whereas testosterone treatment of castrated SHRs increased mean arterial pressure significantly. The dose-response curves to NE and AVP obtained in isolated perfused kidneys from castrated SHRs were displaced to the right of those obtained in sham-operated and castrated + testosterone-treated SHRs. Fasudil treatment produced a rightward shift in the dose-response curves for each agonist in all of the groups and greatly attenuated the differences in renal vascular reactivity to NE and AVP among the 3 groups of SHRs.Collectively, these findings indicate that androgen modulation of hypertension development in the SHR involves a fasudil-sensitive pathway and suggest that further study is warranted in this area.

Topics: Androgens; Animals; Hypertension; Kidney; Male; Potassium Chloride; Rats; Rats, Inbred SHR; rho GTP-Binding Proteins; Vasoconstrictor Agents; Vasopressins

Liddle's syndrome is a genetic form of hypertension linked to Na(+) retention caused by activating mutations in the COOH terminus of the beta or gamma subunit of the epithelial sodium channel (ENaC). In this study, we used the short-circuit current (I(sc)) method to investigate the effects of deamino-8-d-arginine vasopressin (dDAVP) on Na(+) and Cl(-) fluxes in primary cultures of cortical collecting ducts (CCDs) microdissected from the kidneys of mice with Liddle's syndrome carrying a stop codon mutation, corresponding to the beta-ENaC R(566) stop mutation (L) found in the original pedigree. Compared to wild-type (+/+) CCD cells, untreated L/+ and L/L CCD cells exhibited 2.7- and 4.2-fold increases, respectively, in amiloride-sensitive (Ams) I(sc), reflecting ENaC-dependent Na(+) absorption. Short-term incubation with dDAVP caused a rapid and significant increase (approximately 2-fold) in Ams I(sc) in +/+, but not in L/+ or L/L CCD cells. In sharp contrast, dDAVP induced a greater increase in 5-nitro-2-(3-phenylpropamino)benzoate (NPPB)-inhibited apical Cl(-) currents in amiloride-treated L/L and L/+ cells than in their +/+ counterparts. I(sc) recordings performed under apical ion substituted conditions revealed that the dDAVP-stimulated apical secretion of Cl(-), which was absent in cultured CCDs lacking CFTR, was 1.8-fold greater in L/+ and 3.7-fold greater in L/L CCD cells than in their +/+ CCD counterparts. After the basal membrane had been permeabilized with nystatin and a basal-to-apical Cl(-) gradient had been imposed, dDAVP also stimulated larger Cl(-) currents across L/L and L/+ CCD layers than +/+ CCD layers. These findings demonstrate that vasopressin stimulates greater apical CFTR Cl(-) conductance in the renal CCD cells of mice with Liddle's syndrome than in wild-type mice. This effect could contribute to the enhanced NaCl reabsorption observed in the distal nephron of patients with Liddle's syndrome.

Topics: Animals; Cells, Cultured; Chloride Channel Agonists; Chloride Channels; Chlorides; Codon; Cystic Fibrosis Transmembrane Conductance Regulator; Deamino Arginine Vasopressin; Electrophysiology; Epithelial Sodium Channels; Hypertension; Kidney Tubules, Collecting; Mice; Mice, Knockout; Nephrons; Nystatin; Organ Culture Techniques; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium; Sodium Channels; Syndrome; Vasopressins

We compared renal interlobar arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) in terms of cytochrome P450 (CYP) 4A and CYP2E1 protein expression; levels of 20-HETE, 19-HETE, and 18-HETE; and responsiveness to phenylephrine in the absence and presence of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 30 mumol/L), a CYP4A inhibitor. Relative to data in WKY, arteries of SHR exhibited diminished (P<0.05) CYP2E1 and levels of 19-HETE (66.7+/-6.0 versus 44.9+/-2.8 pmol/mg) and 18-HETE (13.8+/-1.6 versus 7.9+/-0.5 pmol/mg), whereas CYP4A and 20-HETE levels (99.3+/-9.1 versus 98.9+/-12.8 pmol/mg) were unchanged. Phenylephrine contracted vascular rings of SHR and WKY; the R(max) was similar in both strains, but SHR vessels were more sensitive as denoted by the lower (P<0.05) EC50 (0.28+/-0.07 versus 0.71+/-0.12 mumol/L). DDMS decreased 20-HETE and, to a lesser extent, 19-HETE, while increasing (P<0.05) the EC50 for phenylephrine by 475% and 54% in vessels of SHR and WKY, respectively. The desensitizing effect of DDMS was reversed by 20-HETE. Notably, the minimal concentration of 20-HETE that decreased the EC50 for phenylephrine in DDMS-treated vessels was smaller in SHR (0.1 micromol/L) than WKY (10 micromol/L), and the sensitizing effect of 20-HETE was blunted (P<0.05) by the (R) stereoisomers of 19-HETE and 18-HETE. We conclude that the increased sensitivity to phenylephrine in arteries of SHR is attributable to a vasoregulatory imbalance produced by a deficit in vascular CYP2E1-derived products, most likely 19(R)-HETE and 18(R)-HETE, which condition amplification of the sensitizing action of 20-HETE.

Topics: Amides; Animals; Arachidonic Acid; Cytochrome P-450 CYP2E1; Cytochrome P-450 CYP4A; Hydroxyeicosatetraenoic Acids; Hypertension; Phenylephrine; Potassium Channel Blockers; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Artery; Sulfones; Tetraethylammonium; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Spontaneously hypertensive rats (SHR) pathologically elevate blood pressure with age. This elevation is accompanied by specific neuronal degeneration in the hypothalamus and enlargement of the lateral ventricles. The aim of this study was to assess the neuroprotective effect of the monoamine oxidase B (MAO-B) inhibitor, rasagiline on paraventricular (PVN) hypothalamic degeneration in SHR. The S-enantiomer of rasagiline, S-PAI, a much weaker MAO inhibitor, and two antihypertensive drugs, captopril and hydralazine were also tested. Normotensive Wistar Kyoto (WKY) rats served as controls. One month-old SHR or WKY rats were treated daily for 3-4 months. Systolic blood pressure was recorded, parvocellular vasopressin (VP) immunopositive cells were counted and the area of the third ventricle measured. In saline-treated SHR, blood pressure rose significantly and the number of VP parvocellular cells was reduced by about 60% relative to WKY. Rasagiline, 1 mg/kg/day, reduced PVN neuronal cell death in SHR up to 112% relative to saline-treated SHR; 0.3 mg/kg/day exerted a smaller but significant effect. These actions were accompanied by parallel reductions in systolic blood pressure. Captoril, hydralazine and S-PAI did not prevent death of VP neurons. In SHR, the volume of the third ventricle was about double that of WKY. Rasagiline significantly prevented this ventricular dilation. These results indicate than rasagiline protects from cell death in an in vivo animal model in a dose-dependant manner and could be of use as a neuroprotector in the central nervous system.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension; Indans; Male; Monoamine Oxidase Inhibitors; Nerve Degeneration; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Wistar; Third Ventricle; Treatment Outcome; Vasopressins

To identify defects in the salt-sensitive Dahl rat (Dahl-S), the natriuretic, catecholaminergic and pressor responses to 60-min elevation of the cerebroventricular sodium concentration (CNS-induced natriuresis) were compared between prehypertensive salt-sensitive Dahl-S and salt-resistant Dahl rats (Dahl-R). The plasma concentrations of the rat natriuretic hormone oxytocin, which has implications for the development of hypertension, and vasopressin (AVP) were also measured. Basal sodium and catecholamine excretion and mean arterial blood pressure (MAP) were similar in both strains. Sodium excretion during CNS stimulation increased more than 15-fold in Dahl-R but only 10-fold in Dahl-S. Dopamine excretion increased only transiently and similarly in both strains. Noradrenaline excretion and response to CNS stimulation were similar, suggesting a comparable sympathetic nervous activity between the strains. MAP increased comparably in Dahl-R and Dahl-S. Plasma AVP concentration was similar in both strains while plasma oxytocin concentration after CNS stimulation was more than 2-fold higher in Dahl-S than in Dahl-R. In conclusion, the prehypertensive Dahl-S has an attenuated natriuretic response to elevations of the cerebroventricular fluid sodium concentration and a higher plasma level of the natriuretic hormone oxytocin. Dopamine is not a mediator of CNS-induced natriuresis in neither strain. The attenuated natriuretic response may partly explain the salt-sensitivity in Dahl-S, and the higher plasma oxytocin value may either represent an effort to compensate for the deficient natriuretic response or reflect a primary defect in this system. Due to the known involvement of oxytocin in central MAP regulation in some hypertensive animal models, the findings warrant further investigation.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Cerebrospinal Fluid; Dopamine; Hypertension; Male; Natriuresis; Norepinephrine; Oxytocin; Rats; Rats, Inbred Dahl; Saline Solution, Hypertonic; Sodium; Vasopressins

Improper functioning of kidneys plays a significant part in the development and further worsening of hypertension. The author aimed at studying the functional and hormonal activity of kidneys in patients with I-III stage essential hypertension under physiological hyperhydratation. 68 patients with essential hypertension and 21 patients of a control group have been observed. The blood content of hormones was detected before and after the physiological water stress consisting 2% of body weight. They are the following: rennin, angiotensin, aldosterone, vasopressin, and atrial sodium-releasing hormone. The observed patients with I stage essential hypertension mostly have their kidneys' ducts apparatus reconstructed with considerable decrease in water reabsorption in ducts apparatus of kidneys. It came along with high level of sodium excretion and moderate activation of rennin-angiotenstin-aldosterone system. Patients with II and III stage essential hypertension responds to the physiological water stress (in contrast to patients with I stage essential hypertension and patients of the control group) with progressive increase in water reabsorption in ducts apparatus of kidneys, decrease in sodium excretion comes along with high level of aldosterone, vasopressin and atrial sodium-releasing hormones.

Topics: Aldosterone; Atrial Natriuretic Factor; Diuresis; Hormones; Humans; Hypertension; Kidney; Kidney Function Tests; Middle Aged; Renin; Vasopressins

Mineralocorticoid effects in the brain include the control of cardiovascular functions, induction of salt appetite, interaction with the vasoactive neuropeptides arginine vasopressin (AVP) and angiotensin II and development or aggravation of hypertension. In this regard, mineralocorticoids may play a pathogenic role in rats with a genetic form of hypertension (spontaneously hypertensive rats, SHR). Our objective was to compare the response of the hypothalamic vasopressinergic system to mineralocorticoid administration in SHR and control Wistar-Kyoto (WKY) rats. Sixteen-week-old male SHR showing a systolic blood pressure of 190 +/- 5 mm Hg and normotensive WKY rats (130 +/- 5 mm Hg) were treated subcutaneously with oil vehicle or a single 10-mg dose of deoxycorticosterone acetate (DOCA). After 2 h, rats were sacrificed and brains prepared for immunocytochemistry of Fos and vasopressin V1a receptor (V1aR) and for non-isotopic in situ hybridization of AVP mRNA. In the basal state, SHR demonstrated a higher number of AVP mRNA- and V1aR-immunopositive cells in the magnocellular division of the paraventricular hypothalamic nucleus (PVN) than WKY rats. After DOCA injection, SHR responded with a significant increase in both parameters with respect to vehicle-injected SHR. In WKY rats, DOCA was without effect on AVP mRNA although it increased the number of V1aR-positive cells. Changes in the number of Fos-positive nuclei were measured in the PVN, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT), a circumventricular region showing anatomical connections with the PVN. In vehicle-injected rats, the PVN of SHR showed a higher number of Fos-positive nuclei than in WKY rats, whereas after DOCA treatment, a significant increment occurred in the OVLT but not in the PVN or MnPO of the SHR group only. These data suggest that the enhanced response of the vasopressinergic system to mineralocorticoids may contribute to the abnormal blood pressure of SHR.

Topics: Animals; Arginine Vasopressin; Desoxycorticosterone; Disease Models, Animal; Hypertension; Hypothalamus; Immunohistochemistry; In Situ Hybridization; Male; Mineralocorticoids; Oncogene Proteins v-fos; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Vasopressin; RNA, Messenger; Vasopressins

Vasopressin (AVP), an antidiuretic hormone, is known to induce hypervolemia and to regulate the renal expression of aquaporin-2 (AQP2) water channels, but it is not yet known whether the latter are involved in the pathogenesis of essential hypertension. The aim of the present study was therefore to make a comparative study of blood pressure (BP), urinary volume (UV), urinary osmolarity (uOsm), urinary AQP2 (uAQP2), and plasma AVP levels (PAVP) in male spontaneously hypertensive rats (SHR; n = 30) at 3, 7, and 12 weeks of age and in male Wistar-Kyoto rats (WKY, n = 30), also after the subcutaneous administration of OPC-31260 (OPC), a human AVP V(2) receptor antagonist. At 3 weeks, SHR had markedly higher uOsm and lower UV levels than WKY. At 7 weeks, SHR were hypertensive, showing increased uAQP2, PAVP, and uOsm levels and a decreased UV. At 12 weeks, no significant changes were observed in this condition. At 7 and 12 weeks of age, OPC-treated WKY rats showed significant reduction in BP and uOsm and increase in UV with respect to untreated animals. From 3 weeks of age, OPC-treated SHR presented significantly lower BP levels, higher UV levels, and lower uOsm than untreated animals. In treated WKY and SHR, uAQP2 levels were lower than in untreated animals. The PAVP appeared to be higher in OPC-treated rats from both strains. These findings suggest that AVP and the AQP2 are involved in the pathogenesis of hypertension in SHR.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Aquaporin 2; Aquaporins; Benzazepines; Biomarkers; Blood Pressure; Disease Models, Animal; Hypertension; Male; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasopressins

The present study was performed to evaluate the hypersensitivity to vasoconstrictors in coronaries from uninephrectomized hypertensive rats (HTR), after a 2-week deoxycorticosterone acetate (DOCA)-salt treatment, in comparison with uninephrectomized age-matched normotensive rats (NTR).. Coronary resistance was recorded from isolated Langendorff hearts perfused at a constant flow rate.. Cumulative dose-response curves to vasopressin, angiotensin II and endothelin in HTR showed an enhanced maximal response, in comparison with NTR (P< 0.05). In contrast, the sensitivity to U-46619, a thromboxane-mimetic agonist, was reduced in HTR in comparison with NTR (P< 0.05). In the presence of ET(A)/ET(B)-receptor antagonists, LU-302 872 (10 micromol/l) and PD-142 893 (0.1-1 micromol/l), cumulative dose-response curves to vasopressin and angiotensin II showed a reduced maximal response in HTR compared with NTR (P< 0.05). LU-302 872 did not change the responsiveness to U-46619 in both groups. Perfusion of hearts from NTR with a subpressor concentration of endothelin-1 (10 pmol/l) potentiated the responsiveness to vasopressin and angiotensin II, but not that of U-46619 (P< 0.05). Hypertension did not alter the dose-response curves obtained with phorbol 12-myristate 13-acetate, an activator of protein kinase C, Bay K 8644, a L-type calcium-channel activator, and KCl. Measurement of endothelin release by radioimmunoassay in the coronary effluent, before and during dose-response curves to vasopressin, angiotensin II and U-46619, showed no significant increase by the vasoconstrictors, although basal endogenous endothelin was increased in HTR (P< 0.05).. Two-week DOCA-salt hypertension is associated with enhanced coronary vasoconstrictor effects of endothelin, vasopressin and angiotensin II. An increased basal release of endogenous endothelin in coronaries from HTR, along with an enhanced responsiveness of the coronary smooth muscle to endothelin, may contribute to the potentiated response to vasoconstrictors. L-type calcium-channels and protein kinase C are not involved in this increased coronary reactivity to vasoconstrictors in HTR.

Topics: Angiotensin II; Animals; Coronary Circulation; Desoxycorticosterone; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Heart; Hypertension; In Vitro Techniques; Male; Nephrectomy; Oligopeptides; Propionates; Pyrimidines; Rats; Rats, Sprague-Dawley; Signal Transduction; Sodium Chloride; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

We have recently reported that endothelin-1 (ET-1), which is increased in the arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, stimulates superoxide production. However, the humoral mechanisms responsible for ET-1-induced superoxide formation in low-renin models of hypertension, such as DOCA-salt hypertension, remain undefined. Vasopressin is known to upregulate vascular preproET-1 gene expression in DOCA-salt rats, an effect that is absent in vasopressin-deficient Brattleboro rats treated with DOCA-salt. The present study tested the hypothesis that vasopressin contributes to ET-1-induced vascular superoxide production in DOCA-salt hypertensive rats. Carotid arterial segments of DOCA, sham (uninephrectomized), or normal (untreated) rats were used for the study. In vitro vasopressin treatment of carotid arteries from normal rats for 24 hours, but not 4 hours, increased both ET-1 and superoxide levels. The increase of vasopressin-induced superoxide was reduced by pretreatment of the vessels with ABT627, a selective ETA receptor antagonist ABT627. Vasopressin, ET-1, and superoxide levels were significant elevated in carotid arteries of DOCA-salt rats compared with sham controls. The selective V1-vasopressin receptor antagonist (beta-Mercapto-beta, beta-cyclopentamethylenepropiony1, O-Me-Tyr2, Arg8 vasopressin, ME-AVP), decreased superoxide both in vasopressin-treated vessels of normal rats and in vessels of DOCA-salt rats, with a concomitant reduction of ET-1 content. These results suggest that vasopressin increases vascular superoxide levels by stimulating ET-1 formation in mineralocorticoid hypertension, and that V1-vasopressin receptors play an important role in this process.

Topics: Animals; Carotid Arteries; Desoxycorticosterone; Endothelin-1; Hypertension; Male; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Superoxides; Vasopressins

In normotensive Wistar rats, vasopressin may act as an excitatory neurotransmitter at synapses of paraventricular neurones on rostral ventrolateral medullary vasomotor neurones. We studied the influence of this neurotransmitter in spontaneously hypertensive rats to determine if it contributed to the increases in sympathetic nerve traffic in these rats.A five-barrel micropipette assembly was used for extracellular recording of neuronal activity and for microiontophoresis of drugs into the vicinity of identified medullary vasomotor neurones. Excitatory effects of iontophoretically applied vasopressin were blocked by simultaneous iontophoretic application of V(1a) antagonist. Similar application of the vasopressin receptor antagonist did not block an excitatory effect of iontophoretically applied glutamate. Excitatory effects produced by activating paraventricular neurones were also blocked by the V(1a) antagonist. However, the vasopressin antagonist did not alter the ongoing activity of medullary vasomotor neurones. Therefore, in these anaesthetised hypertensive rats, we concluded that vasopressin neurones do not exert a significant tonic drive to rostral ventrolateral medullary-spinal vasomotor neurones.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Cardiovascular System; Glutamic Acid; Hypertension; Iontophoresis; Medulla Oblongata; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Wistar; Sympathetic Nervous System; Vasoconstrictor Agents; Vasomotor System; Vasopressins

Abnormal patterns of diurnal blood pressure variation have been reported to be related to advanced target organ damage and poor cardiovascular prognosis. We studied silent cerebrovascular disease and stroke events in older Japanese patients with different nocturnal blood pressure dipping. There was a J-shaped relationship of nocturnal dipping status with silent cerebral infarcts detected by brain magnetic resonance imaging at baseline, and with stroke incidence during the follow-up period. The extreme-dippers (with marked nocturnal blood pressure dipping) and the risers (with higher nocturnal blood pressure than awake blood pressure) had a higher prevalence of silent cerebral infarcts and a poorer stroke prognosis than those with appropriate nocturnal blood pressure dipping (dippers). The extreme-dippers tended to have predominant systolic hypertension and increased blood pressure variability. Several factors affect the diurnal blood pressure variation pattern. The non-dipping pattern is associated with autonomic nervous dysfunction and poor sleep quality due to nocturnal behavior and sleep apnea. The extreme-dippers might have increased arterial stiffness with reduced circulating blood volume in addition to an excessive morning surge due to alpha-adrenergic hyperactivity. Anti-hypertensive medication that normalizes the diurnal blood pressure variation might improve the cardiovascular prognosis in high-risk hypertensive patients.

Topics: Aged; Aged, 80 and over; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cerebrovascular Disorders; Circadian Rhythm; Follow-Up Studies; Humans; Hypertension; Hypotension; Middle Aged; Stroke; Vasopressins

The ability of middle cerebral arteries (MCAs) to utilize intracellular smooth muscle (SM) Ca2+ to produce constriction in response to pressure and agonists was assessed in relation to hemorrhagic stroke development in Wistar-Kyoto stroke-prone (SHRSP) and stroke-resistant (srSHR) spontaneously hypertensive rats.. MCAs were studied with the use of a pressure myograph at 100 mm Hg.. MCAs from srSHR and prestroke SHRSP exhibited pressure-dependent constriction and constricted in response to vasopressin or serotonin in the presence of nifedipine or the absence of [Ca2+]o. MCAs from poststroke SHRSP lost the latter functions and could only constrict in response to vasopressin/serotonin in Krebs' solution containing Ca2+ in the absence of nifedipine. This indicated that the SM could not utilize internal Ca2+ for constriction and maintained constriction by Ca2+ entry through L-type channels. The MCAs of poststroke SHRSP could not constrict to [K+]o-induced depolarization, suggesting that the agonist-induced opening of the L-type channels occurred by mechanisms other than SM depolarization. Depletion of the sarcoplasmic SM Ca2+ stores of MCAs from srSHR with cyclopiazonic acid did not prevent pressure-dependent constriction.. Stroke in SHRSP produced a defect in the ability of MCAs to constrict in response to vasopressin or serotonin via the use of an intracellular source of Ca2+. This could be promoted by an inability of the SM to release intracellular Ca2+, by the depletion of internal Ca2+ stores, or by a decrease in the contractile sensitivity to Ca2+ released from the internal stores.

Topics: Animals; Blood Pressure; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Disease Models, Animal; Disease Progression; Hypertension; In Vitro Techniques; Middle Cerebral Artery; Muscle, Smooth, Vascular; Myography; Nifedipine; Potassium; Rats; Rats, Inbred SHR; Serotonin; Sodium, Dietary; Stroke; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Liddle's syndrome is a monogenic form of hypertension caused by mutations in the PY motif of the COOH terminus of beta- and gamma-epithelial Na+ channel (ENaC) subunits. These mutations lead to retention of active channels at the cell surface. Because of the critical role of this PY motif in the stability of ENaCs at the cell surface, we have investigated its contribution to the ENaC response to aldosterone and vasopressin. Mutants of the PY motif in beta- and gamma-ENaC subunits (beta-Y618A, beta-P616L, beta-R564stop, and gamma-K570stop) were stably expressed by retroviral gene transfer in a renal cortical collecting duct cell line (mpkCCDcl4), and transepithelial Na+ transport was assessed by measurements of the benzamil-sensitive short-circuit current (Isc). Cells that express ENaC mutants of the PY motif showed a five- to sixfold higher basal Isc compared with control cells and responded to stimulation by aldosterone (10(-6) M) or vasopressin (10(-9) M) with a further increase in Isc. The rates of the initial increases in Isc after aldosterone or vasopressin stimulation were comparable in cells transduced with wild-type and mutant ENaCs, but reversal of the effects of aldosterone and vasopressin was slower in cells that expressed the ENaC mutants. The conserved sensitivity of ENaC mutants to stimulation by aldosterone and vasopressin together with the prolonged activity at the cell surface likely contribute to the increased Na+ absorption in the distal nephron of patients with Liddle's syndrome.

Topics: Aldosterone; Amiloride; Animals; Cell Line; Electric Conductivity; Epithelial Cells; Gene Expression; Humans; Hypertension; Mice; Mutation; Sodium Channels; Syndrome; Vasopressins

1. Two clinical studies are reported which investigate: (1) the regulation of vasopressin release in moderate hypertensive subjects not under treatment compared to normotensives and, (2) the effects of antihypertensive treatment on vasopressin and on its osmoregulation in moderate hypertensives. 2. In the first study two stimuli facilitating vasopressin release (active upright position and hypertonic saline infusion) and a stimulus inhibiting vasopressin release (hypotonic saline infusion) have been applied to 13 moderate essential hypertensives and 8 control normotensives. In the second study, limited to hypertensives, the effects on plasma vasopressin and other plasma and urine variables, of either acute (by clonidine, n = 6 or by sodium nitroprusside, n = 6) or chronic (antihypertensive treatment for 1 month, n = 8) blood pressure lowering, before and after the i.v. administration of a hypertonic NaCl solution, were investigated. 3. Baseline plasma vasopressin was not different in hypertensive and in normotensive subjects. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels with no difference between the two groups. Acute, but not chronic, lowering of blood pressure increased plasma vasopressin from 1.6 +/- 0.63 to 3.4 +/- 0.7 pg/mL (p < 0.05); administration of hypertonic saline further increased vasopressin to 10.8 +/- 2.22 (p < 0.01) in the acute and to 6.0 +/- 1.03 pg/mL (p < 0.01) in the chronic study. 4. No significant alterations of the regulation of vasopressin have been found in moderate, uncomplicated hypertension. Moreover, acute lowering of blood pressure facilitated the release of vasopressin and its osmoregulation while a chronic antihypertensive treatment did not interfere with a normal control of vasopressin secretion.

Topics: Antihypertensive Agents; Blood Pressure; Clonidine; Female; Humans; Hypertension; Hypothalamo-Hypophyseal System; Hypotonic Solutions; Male; Middle Aged; Nitroprusside; Posture; Saline Solution, Hypertonic; Vasopressins; Water-Electrolyte Balance

1. The level of mRNA expression of epithelial sodium channel (ENaC) subunits was studied in a salt-dependent hypertensive rat strain (Sabra). These rats exhibit high vasopressin levels compared with their normotensive counterparts. We also investigated whether this expression is influenced by changes in the sodium intake/aldosterone axis or in the fluid intake/vasopressin axis. 2. A higher expression of beta- and gamma-subunit mRNA was found in salt-sensitive compared with salt-resistant rats on a normal salt diet. A high-sodium diet did not alter mRNA abundance in either substrain. In contrast, water supplementation in salt-sensitive rats fed the high-sodium diet induced a marked reduction in mRNA abundance of beta- and gamma-subunits. 3. The present study provides evidence that beta- and gamma-subunits of ENaC are differently expressed in the kidney of salt-sensitive and salt-resistant Sabra rats and that their abundance is regulated by vasopressin, not by sodium intake. These results are consistent with the hypothesis that increased vasopressin-dependent ENaC expression and activity may contribute to the pathogenesis of hypertension in salt-sensitive Sabra rats.

Topics: Aldosterone; Animals; Disease Models, Animal; Drinking; Epithelial Cells; Hypertension; Kidney Cortex; Male; Protein Subunits; Rats; Rats, Inbred Strains; RNA, Messenger; Sodium Channels; Sodium Chloride, Dietary; Time Factors; Up-Regulation; Vasopressins

To study levels of vasoactive hormones and urinary excretion of sodium and potassium between groups of Greenland Inuit and Danes, and to analyse the relationship between these hormones and 24-h blood pressure, including nightly blood pressure dips and pulse pressure.. 145 Greenlandic participants were categorized in three groups according to degree of westernization, based on dietary habits and current place of residence; 41 Danes were included as controls. Twenty-four-hour blood pressure was measured. Venous plasma concentrations of vasoactive hormones were measured. Urine was collected for 24 hours for analysis of excretion of sodium and potassium.. The Inuit population of Greenland had a lower diastolic blood pressure, a higher pulse pressure and lower nocturnal blood pressure dip than Danes had. Angiotensin II in plasma and urine excretion of potassium were higher among Greenlanders compared with Danes, irrespective of diet and place of residence. Aldosterone and urine excretion of sodium were significantly higher among participants in Denmark compared with participants in Greenland. Brain natriuretic peptide and atrial natriuretic peptide were independently and negatively associated with diastolic blood pressure, and vasopressin was positively associated with systolic blood pressure and pulse pressure. Ethnic differences in the effect of vasoactive hormones or urinary sodium and potassium excretion could not explain the difference in blood pressure.. It is suggested that a high dietary intake of potassium and low sodium intake among Greenlanders may affect blood pressure. Further attention should be drawn to the occurrence of high pulse pressure and high activity in the renin-angiotensin system in Inuit populations.

Topics: Aldosterone; Angiotensin II; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Denmark; Epidemiologic Studies; Ethnicity; Feeding Behavior; Female; Greenland; Humans; Hypertension; Inuit; Male; Natriuretic Peptides; Potassium; Renin-Angiotensin System; Sodium; Topography, Medical; Vasopressins

Dahl salt-sensitive (DSS) rats fed an 8.7% sodium chloride diet from weaning spontaneously developed hypertension and a 50% mortality rate by 5 weeks. Before death the rats exhibited behavioural signs of stroke and disruption of the blood-brain barrier.. To test the hypothesis that rats exhibiting stroke had middle cerebral arteries (MCAs) that had lost the ability to constrict in response to pressure, and to assess whether this defect was associated with abnormalities in protein kinase C (PKC)-mediated constriction.. MCAs were sampled from DSS rats before and after stroke and from Dahl salt-resistant (DSR) rats fed 8.7% NaCl. Constrictions in response to a 100 mmHg pressure step and to PKC activation by phorbol dibutyrate (PDB) (0.1 micromol/l) in the presence of nifedipine (3 micromol/l) were measured.. MCAs from DSS rats after stroke constricted in response to vasopressin but were unable to constrict in response to pressure or PDB in the presence of nifedipine, whereas those from DSS rats before stroke and from DSR rats constricted in response to all the stimuli. The PKC inhibitors, chelerythrine (12 micromol/l) and bisindolylmaleimide (5 micromol/l) inhibited constrictions in response to pressure and to PDB in the presence of nifedipine.. Constriction of the MCA in response to pressure is dependent on functional PKC signalling. Development of stroke in DSS rats fed a high-salt diet is associated with an inability of the MCAs to constrict in response to pressure, possibly because of the presence of an incompetent PKC system. The inability to constrict in response to pressure may cause blood flow abnormalities that contribute to disruption of the blood-brain barrier in these rats.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Cerebrovascular Disorders; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension; Middle Cerebral Artery; Models, Cardiovascular; Nifedipine; Protein Kinase C; Rats; Rats, Inbred Dahl; Sodium Chloride, Dietary; Stroke; Survival Analysis; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Dopamine is an important transmitter in the CNS and PNS, critically regulating numerous neuropsychiatric and physiological functions. These actions of dopamine are mediated by five distinct receptor subtypes. Of these receptors, probably the least understood in terms of physiological functions is the D5 receptor subtype. To better understand the role of the D5 dopamine receptor (DAR) in normal physiology and behavior, we have now used gene-targeting technology to create mice that lack this receptor subtype. We find that the D5 receptor-deficient mice are viable and fertile and appear to develop normally. No compensatory alterations in other dopamine receptor subtypes were observed. We find, however, that the mutant mice develop hypertension and exhibit significantly elevated blood pressure (BP) by 3 months of age. This hypertension appears to be caused by increased sympathetic tone, primarily attributable to a CNS defect. Our data further suggest that this defect involves an oxytocin-dependent sensitization of V1 vasopressin and non-NMDA glutamatergic receptor-mediated pathways, potentially within the medulla, leading to increased sympathetic outflow. These results indicate that D5 dopamine receptors modulate neuronal pathways regulating blood pressure responses and may provide new insights into mechanisms for some forms of essential hypertension in humans, a disease that afflicts up to 25% of the aged adult population in industrialized societies.

Topics: Adrenal Glands; Animals; Blood Pressure; Brain; Brain Chemistry; Epinephrine; Gene Targeting; Hypertension; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Knockout; Norepinephrine; Oxytocin; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D5; Receptors, Oxytocin; Receptors, Vasopressin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sympathetic Nervous System; Vasopressins

Levels of vasopressin, aldosterone and plasma renin activity were studied in patients with arterial hypertension. It is shown that progression of the disease dysregulates neurohormonal systems responsible for arterial pressure control. Activation of vasoconstrictive systems of vasopressin and aldosterone synthesis involved in retention of fluid in the body goes in parallel to lowering of renin secretion. The above changes may be considered as a compensatory mechanism of arterial hypertension stabilization.

Topics: Adult; Aldosterone; Female; Humans; Hypertension; Male; Middle Aged; Renin; Renin-Angiotensin System; Vasopressins

Inbred borderline-hypertensive Hiroshima rats (BHR) of the Wistar strain established in our laboratory are characterized by elevated plasma levels of vasopressin (Teranishi et al.: Jpn J Pharmacol 1999; 79: 251-255). To investigate the role of endogenous vasopressin in hypertension in BHR, we assessed the effect of a selective vasopressin V1 receptor antagonist (V1A) on regional hemodynamics using an electromagnetic flowmeter. The basal values of mean arterial pressure, heart rate, and regional resistances of renal and hindquarter vascular beds in conscious BHR were significantly higher than those in normotensive control rats (NCR). Injection of V1A (10 microg/kg) did not appreciably affect the hemodynamics in either animal. Successive administration of V1A after ganglionic blockade with hexamethonium bromide (C6; 25 mg/kg), however, significantly attenuated renal, mesenteric and hindquarter resistances in BHR but not in NCR. The hypotensive effect of V1A after sympathoinhibition was significantly greater in BHR than in both NCR and spontaneously hypertensive rats. However, the hypotensive effect induced by V1A was diminished only in BHR pretreated with a ganglionic blockade followed by injection of captopril (1 mg/kg). These findings indicate that BHR could be used as a new hypertensive model with an abnormality in endogenous vasopressin-mediated vasoconstriction appearing in the presence of angiotensin II after sympathoinhibition.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Captopril; Ganglionic Blockers; Hemodynamics; Hexamethonium; Hypertension; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Wistar; Vasopressins

The signaling cascades responsible for the activation of transcription factors in the hypertrophic growth of cardiac myocytes during hemodynamic overload are largely unknown. Several of the genes upregulated in the hypertrophied heart, including B-type natriuretic peptide (BNP) gene, are controlled by the cardiac-restricted zinc finger transcription factor GATA4.. An in vivo model of intravenous administration of arginine(8)-vasopressin (AVP) for up to 4 hours in conscious normotensive rats was used to study the signaling mechanisms for GATA activation in response to pressure overload. Gel mobility shift assays were used to analyze the trans-acting factors that interact with the GATA motifs of the BNP promoter. AVP-induced increase in mean arterial pressure was followed by a significant increase in the BNP and c-fos mRNA levels in both the endocardial and epicardial layers of the left ventricle, whereas GATA4 and GATA6 mRNA levels remained unchanged. Pressure overload within 15 to 60 minutes produced an increase in left ventricular BNP GATA4 but not GATA5 and GATA6 binding activity, and at 30 minutes a 2.2-fold increase (P:<0.001) in GATA4 binding was noted. The mixed endothelin-1 ET(A)/ET(B) receptor antagonist bosentan but not the angiotensin II type 1 receptor antagonist losartan completely inhibited the pressure overload-induced increase in left ventricular BNP GATA4 binding activity. Bosentan alone had no statistically significant effect on GATA4 binding activity of the left ventricle in conscious animals.. ET-1 is a signaling molecule that rapidly upregulates GATA4 DNA binding activity in response to pressure overload in vivo.

Topics: Analysis of Variance; Animals; Arginine; Cells, Cultured; Disease Models, Animal; DNA; DNA-Binding Proteins; Endothelin Receptor Antagonists; Endothelin-1; GATA4 Transcription Factor; GATA6 Transcription Factor; Hypertension; Myocardium; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Signal Transduction; Transcription Factors; Vasopressins; Ventricular Function, Left

Abnormalities in autonomic activity resulting in disturbances of the diurnal rhythm of many physiologic processes were recently revealed in hypertensive patients. These findings suggest deteriorations in the functioning of the suprachiasmatic nucleus (SCN), which is known to be the biological clock of mammals. To test this hypothesis, we carried out an immunocytochemical study of the SCN of primary hypertension patients who had died due to myocardial infarction or brain hemorrhage, and compared them with those of individuals with a normal blood pressure who had never had any autonomic disturbances and died from myocardial infarction after chest trauma or from hypothermia. We found that the staining for the three main neuronal populations of the SCN; i.e., vasopressin, vasoactive intestinal polypeptide, and neurotensin, reduced by more than 50% in the hypertensives compared with controls. The present data indicate a serious dysregulation of the biological clock in hypertensive patients. Such a disturbance may cause a harmful hemodynamic imbalance with a negative effect on circulation, especially in the morning, when the inactivity-activity balance changes. The difficulty in adjusting from inactivity to activity might be involved in the morning clustering of cardiovascular events.

Topics: Adult; Aged; Blood Pressure; Chronobiology Disorders; Circadian Rhythm; Female; Humans; Hypertension; Male; Middle Aged; Neuropeptides; Neurotensin; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

1. The relative roles of endothelin (ET) and vasopressin (AVP) in the regulation of blood pressure (BP), cardiac output (CO) and total peripheral resistance (TPR) were investigated in the early stages (24 - 31 days) of development of hypertension in the conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rat model. 2. BP was recorded with radiotelemetry devices and CO with ultrasonic transit-time probes. TPR was calculated from the BP and CO recordings. The contributions of endogenous ET and AVP were studied by infusing [d(CH(2))(5)(1),O-Me_Tyr(2),Arg(8)]-vasopressin, a V(1)-receptor antagonist, and bosentan, a mixed ET(A)/ET(B) receptor antagonist (Study 1). Vascular responsiveness was estimated from the changes in TPR evoked by i.v. infusions of ET-1 and AVP (Study 2). 3. In study 1, infusion of bosentan reduced TPR and BP dramatically in DOCA-salt hypertensive rats but not in SHAM control rats, and this effect was greater when the AVP system had been blocked. In contrast, the V(1) receptor antagonist alone failed to change TPR and BP in DOCA-salt hypertensive rats. However, subsequent infusion of the V(1) receptor antagonist during the plateau phase of the response in bosentan pretreated DOCA-salt hypertensive rats led to significant decreases in both BP and TPR. 4. In study 2, TPR and BP responses to ET-1, but not AVP, were greater in DOCA-salt rats than in control rats. CO responses to ET-1 or AVP were similar in the two groups. 5. The results suggest that both ET and AVP play a role in the maintenance of TPR and BP; when one system is blocked the other compensates. However, the magnitude of the contribution to the hypertensive state appears greater for ET than for AVP. Enhanced vascular responses to ET appear to contribute to this greater role.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Bosentan; Cardiac Output; Desoxycorticosterone; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Hypertension; Injections, Intravenous; Male; Rats; Rats, Sprague-Dawley; Sulfonamides; Time Factors; Vascular Resistance; Vasopressins

Oxytocin and its receptor are potentially important for cardiovascular functions. In the present paper, we report their chromosome locations in the rat and their comparative mapping with the mouse and human. They are located in chromosome regions previously known to contain quantitative trait loci for blood pressure in various genetic crosses. Thus, they have become valid candidate genes for genetic hypertension.

Topics: Animals; Blood Pressure; Chromosomes, Human, Pair 3; Cricetinae; Humans; Hypertension; Internet; Mice; Oxytocin; Physical Chromosome Mapping; Quantitative Trait, Heritable; Radiation Hybrid Mapping; Rats; Receptors, Oxytocin; Vasopressins

The dynamic of natural antibodies against angiotensin II, bradykinin and vasopressin in blood serum was studied in 75 patients with hypertension and obesity. Universal normalizing effect of the diet consists in decrease of levels of natural antibodies was found.

Topics: Adult; Angiotensin II; Arteriosclerosis; Bradykinin; Diet, Sodium-Restricted; Female; Humans; Hypertension; Immunoenzyme Techniques; Male; Middle Aged; Obesity; Vasopressins

Small mesenteric arteries of spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) were compared for the production of 20-HETE and the effects of 20-HETE and N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS, 30 micromol/L), a 20-HETE synthesis inhibitor, on contractile responsiveness to phenylephrine (0.1 to 50.0 micromol/L). 20-HETE production was higher in vessels of SHR compared with WKY (1.34+/-0.16 versus 0.27+/-0.09 pmol/mg tissue, P<0.05). Phenylephrine elicited concentration-dependent vascular contraction; the R(max) was similar in vessels of SHR and WKY, but the former were more sensitive as denoted by the lower EC(50) (1.10+/-0.14 versus 1.89+/-0.33 micromol/L, P<0.05). DDMS caused a rightward shift in the concentration-response curve to phenylephrine, increasing (P<0.05) the EC(50) by 258% and 134% in vessels of SHR and WKY, respectively. In contrast, in DDMS-treated vessels, 20-HETE (0.01 to 10.0 micromol/L) caused a leftward shift in the phenylephrine concentration-response curve, decreasing (P<0.05) the EC(50) without affecting the R(max). Importantly, the minimal concentration of 20-HETE that decreased the EC(50) of phenylephrine was much smaller in vessels of SHR that of WKY (0.01 versus 1.0 micromol/L). We conclude that 20-HETE increases the sensitivity of mesenteric arterial vessels to phenylephrine, vessels of SHR are more sensitive to this action of the eicosanoid than vessels of WKY, and vessels of SHR produce more 20-HETE than do vessels of WKY. Hence, 20-HETE of vascular origin may be a determinant of the increased reactivity to constrictor agonists in the vasculature of SHR.

Topics: Amides; Animals; Disintegrins; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hydroxyeicosatetraenoic Acids; Hypertension; In Vitro Techniques; Isometric Contraction; Mesenteric Arteries; Muscle, Smooth, Vascular; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Species Specificity; Sulfones; Vasopressins; Viper Venoms

In the present study we have used the detection of Fos, the protein product of c-fos, to determine the distribution of neurons in the medulla and hypothalamus that are activated by changes in central blood volume. Experiments were conducted in both barointact and barodenervated conscious rabbits, to determine the contribution of arterial baroreceptors to the pattern of Fos expression evoked by changes in central blood volume, induced either by intravenous infusion of an isotonic modified gelatin solution, or by partial occlusion of the vena cava. These procedures resulted in a significant increase and decrease, respectively, in right atrial pressure over a 60 min period. In control experiments, barointact and barodenervated rabbits were subjected to the identical procedures except that no changes in central blood volume were induced. In comparison with the control observations, central hypervolaemia produced a significant increase in the number of Fos-immunoreactive neurons in the nucleus tractus solitarius, area postrema, the caudal, intermediate and rostral parts of the ventrolateral medulla, supraoptic nucleus, paraventricular nucleus, arcuate nucleus, suprachiasmatic nucleus and median preoptic nucleus. The overall pattern of Fos expression induced by central hypervolaemia did not differ significantly between barointact and barodenervated animals. Similarly, the overall pattern of Fos expression induced by central hypovolaemia did not differ significantly between barointact and barodenervated animals, but did differ significantly from that produced by hypervolaemia. In particular, central hypovolaemia produced a significant increase in Fos expression in the same regions as above, but also in the subfornical organ and organum vasculosum lamina terminalis. In addition, compared with central hypervolaemia, hypovolaemia produced a significantly greater degree of Fos expression in the rostral ventrolateral medulla and supraoptic nucleus. Furthermore, double-labelling for tyrosine hydroxylase immunoreactivity demonstrated that neurons in the ventrolateral medulla that expressed Fos following hypovolaemia were predominantly catecholamine cells, whereas following hypervolaemia they were predominantly non-catecholamine cells. Finally, double-labelling for vasopressin immunoreactivity demonstrated that the number of Fos/vasopressin immunoreactive cells in the supraoptic nucleus was approximately 10 times greater following hypovolaemia compared with hypervolaemi

Topics: Animals; Aorta; Blood Volume; Cardiovascular Physiological Phenomena; Carotid Sinus; Consciousness; Denervation; Genes, Immediate-Early; Hypertension; Hypotension; Hypovolemia; Male; Neurons; Paraventricular Hypothalamic Nucleus; Pressoreceptors; Proto-Oncogene Proteins c-fos; Rabbits; Solitary Nucleus; Tyrosine 3-Monooxygenase; Vasopressins

Nitric oxide attenuates both vasopressin-induced vasoconstriction and vasopressin release. We tested whether hypertension and renal dysfunction elicited by chronic inhibition of nitric oxide (NO) synthesis using N(G)-nitro-L-arginine (L-NNA) could be mediated in part by vasopressin V(1A) receptors. Male rats were treated orally for 6 weeks with L-NNA (15 mg/kg per day), a nonpeptide V(1A) receptor antagonist (2S)-1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3, 4-dimethoxybenzene-sulfonyl)-3-hydroxy-2, 3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide (SR 49059, 30 mg/kg per day), or a combination of SR 49059 and L-NNA (same doses), or they received no treatment. Both drugs were added to the food. Measurements were performed in conscious rats (urine collection in metabolic cages, tail-cuff arterial pressure) and at the end of the study in anesthetized rats (clearance measurements). L-NNA produced sustained hypertension, decreased glomerular filtration rate, and increased renal vascular resistance, plasma renin activity, and urinary albumin excretion. SR 49059 had no effect per se on these parameters and also did not attenuate the hypertension and renal dysfunction induced by L-NNA. Surprisingly, SR 49059 potentiated L-NNA-induced hypertension at the end of the 6-week treatment. However, the blood pressure response and the renal and mesenteric vasoconstriction elicited by exogenous vasopressin were attenuated in rats treated with SR 49059. L-NNA did not change plasma vasopressin concentration or 24-hour urinary vasopressin excretion. Our findings suggest that activation of vasopressin V(1A) receptors does not contribute to the hypertension and renal dysfunction induced by chronic NO synthesis inhibition. They also document unchanged plasma vasopressin concentration in NO-deficient hypertension.

Topics: Albuminuria; Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Enzyme Inhibitors; Heart; Heart Rate; Hypertension; Indoles; Kidney; Male; Nitric Acid; Nitric Oxide Synthase; Nitroarginine; Organ Size; Pyrrolidines; Rats; Rats, Sprague-Dawley; Systole; Time Factors; Vasopressins

AVP not only increases osmotic water permeability (Pf) in the rat cortical collecting duct (CCD), but also acts synergistically with aldosterone to augment sodium reabsorption (JNa). These effects are inhibited by catecholamines via alpha2 adrenergic receptors, and by dopamine. We review here studies designed to determine the mechanism and receptor involved in dopamine action. The inhibitory effect of dopamine on Na+ and water transport was found to be reversible, and was not produced by agonists specific to D1A and D1B receptors. D2-type (D2, D3 or D4) receptors and activation of the GTP-binding protein Gi were implicated by the observation that dopamine had no inhibitory effect when JNa and Pf were stimulated by a cyclic AMP analogue plus isobutylmethylxanthine. The only dopaminergic antagonist that reversed the inhibitory effect of dopamine was clozapine, which is relatively D4-specific. We also found that dopamine or D1-specific agonists by themselves had no effect on cAMP production. However, dopamine inhibited the high rate of AVP-dependent cAMP production, and this effect of dopamine was reversed by clozapine but not other antagonists or by inhibitors of protein kinase C. The D4 receptor was observed in western blots of renal cortical proteins, and it was localized to the collecting duct by RT-PCR and immuno-histochemistry using a D4-specific antibody. These results show that at least a portion of the natriuretic effect of dopamine can be attributed to inhibition of AVP-dependent Na+ reabsorption by the CCD, and they introduce another signalling system as a candidate in the aetiology of low-renin, salt-dependent hypertension.

Topics: Animals; Arginine Vasopressin; Clozapine; Cyclic AMP; Dopamine; Dopamine Agonists; Dopamine Antagonists; Fenoldopam; Hypertension; In Vitro Techniques; Kidney Tubules, Collecting; Rats; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D4; RNA, Messenger; Vasopressins

Cerebrovascular pressure-dependent constriction (PDC) is associated with smooth muscle (SM) depolarization and Ca(2+) influx through voltage-gated channels. We studied the alterations in electromechanical contraction in the middle cerebral arteries (MCAs) of stroke-prone Wistar-Kyoto spontaneously hypertensive rats (SHRsp) in relation to the stroke-related loss of PDC.. Constriction to pressure, elevated [K(+)](o) and/or [Ca(2+)](o), and SM membrane potentials (E(m)) were measured in isolated pressurized MCAs of SHRsp and stroke-resistant SHR.. MCAs of SHRsp exhibited an age-related decrease in PDC before hemorrhagic stroke and a loss of PDC after stroke. At 100 mm Hg, the MCAs of poststroke SHRsp maintained partial constriction that was not altered with pressure but was inhibited by nifedipine (1 micromol/L). The MCAs of poststroke SHRsp constricted to vasopressin (0.17 micromol/L) but not to elevated [K(+)](o). When pressure was reduced from 100 to 0 mm Hg, the MCAs from young prestroke SHRsp exhibited SM hyperpolarization (-38 to -46 mV), whereas those of poststroke SHRsp maintained a constant, depolarized E(m) (-34 mV). Alterations in E(m) with varying [K(+)](o) suggested that there was a decrease in SM K(+) conductance in the MCAs of poststroke SHRsp.. The observation that the MCAs of poststroke SHRsp depolarize but do not constrict to elevated [K(+)](o) suggests the presence of dysfunctional voltage-gated Ca(2+) channels. The inability to alter E(m) with pressure or to constrict to depolarization could partially contribute to the loss of PDC in the MCAs of poststroke SHRsp.

Topics: Animals; Calcium; Calcium Channel Blockers; Cerebral Arteries; Electrophysiology; Genetic Predisposition to Disease; Hypertension; In Vitro Techniques; Muscle, Smooth, Vascular; Nifedipine; Potassium; Pressure; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reference Values; Stroke; Vasoconstriction; Vasoconstrictor Agents; Vasomotor System; Vasopressins

To analyse the effects of endothelin-1 and vasopressin on the sympathetic vasoconstriction during hypertension.. Electrical field stimulation (4 Hz) was applied to isolated, 2 mm segments of the tail artery from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats prepared for isometric tension recording.. The contraction to electrical stimulation was potentiated by endothelin-1 (10(-10)-10(-8) M) in arteries from WKY but not from SHR, and by vasopressin (10(-12)-10(-10) M) more markedly in arteries from WKY than from SHR. The potentiation by endothelin-1 was reduced more markedly by the antagonist of endothelin ETA receptors BQ-123 (10(-5) M) than by the endothelin ETB receptor antagonist BQ-788 (10(-5) M). The potentiation by vasopressin was reduced by the antagonist of vasopressin V1 receptors d(CH2)5Tyr(Me)AVP (10(-7) M), but not by the vasopressin V2 receptor antagonist d(CH2)5D-Ile2, Ile4AVP (10(-7) M). The blocker of L-type calcium channels verapamil (10(-5) M) reduced the potentiation by both endothelin-1 and vasopressin in arteries from WKY rats, and increased the potentiation by vasopressin in arteries from SHR. Noradrenaline (10(-8)-10(-4) M) contraction was not modified by endothelin-1 (3 x 10(-9) M) or vasopressin (3 x 10(-11) M), and contraction to endothelin-1 (10(-9)-10(-7) M) and vasopressin (10(-10)-10(-7) M) was lower in arteries from SHR than from WKY rats.. (1) The potentiation by endothelin-1 and vasopressin of the sympathetic vasoconstriction, probably due to increased release of noradrenaline, is impaired during hypertension, and (2) this potentiation is mediated mainly by endothelin ETA receptors, and by vasopressin V1 receptors, in both WKY and SHR, and for both peptides it is mediated by L-type calcium channels in arteries from normotensive but not in those from hypertensive animals.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Calcium Channel Blockers; Electric Stimulation; Endothelin Receptor Antagonists; Endothelin-1; Hypertension; In Vitro Techniques; Male; Norepinephrine; Oligopeptides; Peptides, Cyclic; Piperidines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoconstriction; Vasopressins; Verapamil

We tested the hypothesis that hypertension in atrial natriuretic peptide (ANP) knockout mice is caused in part by disinhibition of angiotensin II-mediated vasopressin release. Inactin-anesthetized F(2) homozygous ANP gene-disrupted mice (-/-) and wild-type (+/+) littermates were surgically prepared for carotid arterial blood pressure measurement (ABP) and background intravenous injection of physiological saline or vasopressin V(1)-receptor antagonist (Manning compound, 10 ng/g body wt) and subsequent intracerebroventricular (left lateral ventricle) injection of saline (5 microl) or ANP (0.5 microg) or angiotensin II AT(1)-receptor antagonist losartan (10 microg). Only (-/-) showed significant decrease in ABP after intracerebroventricular ANP or losartan. Both showed significant hypotension after intravenous V(1) antagonist, but there was no difference between their responses. We conclude that 1) vasopressin contributes equally to ABP maintenance in ANP-disrupted mice and wild-type controls; 2) permanently elevated ABP in ANP knockouts is associated with increased central nervous angiotensin II AT(1)-receptor activation; 3) disinhibition of central nervous angiotensin II AT(1) receptors in ANP-deficient animals does not lead to a significant increase in the importance of vasopressin as a mechanism for blood pressure maintenance.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Hormone Antagonists; Hypertension; Injections, Intravenous; Losartan; Male; Mice; Mice, Knockout; Paraventricular Hypothalamic Nucleus; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Vasopressins

The goal of this study was to identify the source of baroreceptor-related noradrenergic innervation of the diagonal band of Broca (DBB). Male Sprague-Dawley rats underwent sinoaortic denervation (SAD, n = 13) or sham SAD surgery (n = 13). We examined Fos expression produced by baroreceptor activation and dopamine-beta-hydroxylase immunofluorescence in hindbrain regions that contain noradrenergic neurons. Baroreceptors were stimulated by increasing blood pressure >40 mmHg with phenylephrine (10 microgram. kg(-1). min(-1) iv) in sham SAD and SAD rats. Controls were infused with 0.9% saline. Only the locus ceruleus (LC) demonstrated a baroreceptor-dependent increase in Fos immunoreactivity in dopamine-beta-hydroxylase-positive neurons. In a second experiment, normal rats received rhodamine-labeled microsphere injections in the DBB (n = 12) before phenylephrine or vehicle infusion. In these experiments, only the LC consistently contained Fos-positive cells after phenylephrine infusion that were retrogradely labeled from the DBB. Finally, we lesioned the LC with ibotenic acid and obtained extracellular recordings from identified vasopressin neurons in the supraoptic nucleus. LC lesions significantly reduced the number of vasopressin neurons that were inhibited by acute baroreceptor stimulation. Together, these results suggest that noradrenergic neurons in the LC participate in the baroreflex activation of the DBB and may thus be important in the baroreflex inhibition of vasopressin-releasing neurons in the supraoptic nucleus.

Topics: Animals; Blood Pressure; Cell Count; Denervation; Diagonal Band of Broca; Dopamine beta-Hydroxylase; Hypertension; Ibotenic Acid; Locus Coeruleus; Male; Medulla Oblongata; Neural Pathways; Neurons; Phenylephrine; Pons; Pressoreceptors; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Sinus of Valsalva; Supraoptic Nucleus; Vasopressins

Topics: Aerospace Medicine; Awards and Prizes; Humans; Hyperbaric Oxygenation; Hypertension; Hypoxia; Professional Competence; Research; Vasopressins

The present study was designed to compare the effects of glucagon-like peptide-1 (7-36) amide (GLP-1) injected centrally or systemically in a dose range of 10-10000 ng on the vasopressin and oxytocin release as well as the blood pressure in the rat. The urethane-anaesthetised Wistar male and female rats were fitted with venous as well as arterial catheters and, in the second study, additionally with the intracerebroventricular cannula. The arterial blood pressure was monitored throughout the experiment. The plasma vasopressin/oxytocin concentrations were measured in blood samples taken 15 min before and 5, 15 and 30 min after the intravenous or intracerebroventricular GLP-1 injection. No gender-dependent differences were seen as to the GLP-1 effect on the blood pressure or the hormone release. GLP-1 administered centrally or systemically at low doses (10 or 100 ng) either showed a hypertensive or biphasic (an increase followed by a decrease in the blood pressure) effect. On the other hand, 1000 or 10000 ng GLP-1 caused a clear increase of the blood pressure regarding the way of injection. When injected systemically, GLP-1 increased the release of both neurohypophysial hormones. When injected centrally, however, GLP-1 either enhanced or, at low doses, significantly reduced the plasma vasopressin/oxytocin levels. The effect on the blood pressure seems to be independent of the possible pressor effect of endogenous vasopressin. It is concluded that GLP-1 may modulate the function of the hypothalamo-neurohypophysial system as well as the cardiovascular system through both the central and systemic mechanisms.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Hypertension; Injections, Intravenous; Male; Neurotransmitter Agents; Oxytocin; Peptide Fragments; Radioimmunoassay; Rats; Rats, Wistar; Sex Factors; Time Factors; Vasopressins

Hypertension is a prevalent health problem and a major cause of morbidity and mortality in the United States. It is one of the most important modifiable risk factors for multiple medical problems including coronary artery disease, congestive heart failure, and end-stage renal disease. There are many efficacious antihypertension medications, each with its own indications and side effect profile. Furthermore, new drugs are being developed rapidly. This article features how to diagnose hypertension as well as describes pharmacological and nonpharmacological treatment options. The properties, proper use, and side effect profile of each of the nine classes of antihypertension drugs commonly used and three classes of medications on the horizon will be described. The purpose of this manuscript is to familiarize physicians with the antihypertension regimens commonly employed and to introduce drugs which may become available in the near future.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Diuretics; Endothelin Receptor Antagonists; Humans; Hypertension; Vasodilator Agents; Vasopressins

The aim of the study was to investigate the effect of two various atherogenic stimuli (vasopressin-induced hypertension or hypercholesterolemia) on the collagen and glycosaminoglycan (GAG) content in the internal or external part of both thoracic and abdominal aorta, which are differently susceptible to atherosclerosis. Experimental rabbits were divided into four groups: controls, animals injected with physiological saline or vasopressin at the dose of 1 IU/kg from the 1 st to the 25 th day of experiment, respectively. The animals from group 4 were maintained on food, containing 0.25% cholesterol. Only in the vasopressin-treated group, the systolic blood pressure was elevated from 110 mmHg at the beginning, to 166 mmHg at the end of the study. After 14 weeks the aorta was dissected into internal and external parts. GAG fractions were separated and estimated as uronic acids. Collagen was evaluated as the hydroxyproline content in the tissue. Augmented total GAG and heparan sulphate (HS) level, plus no changes in the collagen content were seen in the internal part of the thoracic aorta in rabbits with hypercholesterolemia or hypertension. In the hypertensive animals, the changes were extended to the external part of the aorta and, additionally, comprised the elevation of the chondroitin-4 sulphate (C-4S) content. The two atherogenic stimuli increased the collagen level with no elevation of the GAG content in the abdominal aorta. A convergent effect of the injury, caused by hypertension or hypercholesterolemia on the collagen, total GAG and HS content was shown in the respective parts of the rabbit aortas. The common GAG, increased in the thoracic aorta, stand for the HS, in both hypertensive and hypercholesterolemic rabbits. As the sensitivity to atherosclerosis development in different segments of the aorta varies, they express various responses of the connective tissue matrix to injuries, caused by hypertension or hypercholesterolemia.

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; Cholesterol; Collagen; Connective Tissue; Glycosaminoglycans; Hypercholesterolemia; Hypertension; Male; Rabbits; Vasoconstrictor Agents; Vasopressins

Experiments were carried out in male Sprague-Dawley rats. The animals were randomly divided into three groups: control, stressed and stress + captopril. Stress stimulations were composed of repeated electric foot-shock combined with noise, twice one day (2 h each session) for 15 consecutive days. Animals in the stress+captopril group were administered with captopril (50 mg/kg.d) intraperitoneally. The results showed that at the end of the 15-day experiment the systolic pressure of the tail artery in stressed rats was significantly higher than that of the control rats, i.e., 19.75+/ C1.0 kPa (n=8, P<0.05) versus 16.32+/ C0.55 kPa (n=7); the vasopressin (AVP) mRNA level in the hypothalamus of the stressed rats also increased significantly compared with that of the control rats, i.e., 12990.33+/ C1533.58 (n=6, P<0.001) versus 7332.66+/ C522.65 (n=6). However, in the stress + captopril rats, both the tail artery systolic pressure and hypothalamic AVP mRNA level were significantly higher than those of the control rats, but lower than those of the stressed rats. In the control rats, no significant change in mean blood pressure (MBP) was observed after intracerebroventricular (icv) injection of 0.3 microgram of d(CH(2))(5)Tyr(Me)AVP, a selective AVP V(1) receptor antagonist; however, a decrease in MBP was observed in both stressed and stress+captopril rats (P<0.05), but the decrease in stress+captopril rats was more obvious than that of the stressed rats after icv a same dose of d(CH(2))(5)Tyr(Me)AVP. These results indicate that the endogenous renin-angiotensin system participates in the mechanism of the stress-induced high blood pressure in rats, and that the effect of Ang II is mediated mainly by stimulating hypothalamic AVP synthesis and release, which in turn result in an increase in blood pressure by acting on the central V (1) receptors.

Topics: Angiotensin II; Animals; Captopril; Hypertension; Hypothalamus; Male; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stress, Physiological; Vasopressins

We previously demonstrated that the Ren-2 transgenic (TG) rat is sensitive to salt, showing a sodium-induced pressor response. The present studies determined the effect of central stimulation with hypertonic saline (HS) and angiotensin II (Ang II) on mean arterial pressure (MAP), heart rate (HR), and plasma vasopressin. HS (1 mol/L NaCl, 5 microL) or Ang II (100 ng, 5 microL) was injected into the lateral ventricle of conscious male TG and control rats. The pressor responses to HS and Ang were greater in TG than in control rats, increases of 42+/-4 and 41+/-4 mm Hg versus 25+/-3 and 18+/-2 mm Hg (HS and Ang II and TG and control rats, respectively). The TG rats also showed an increased vasopressin response to Ang II, peak levels of 14+/-3 versus 28+/-3 pg/mL (control versus TG rats). HS increased plasma vasopressin levels, although the group responses were not different. HR was not significantly altered by either stimulus. Results demonstrate an increased responsiveness to intraventricular HS and Ang II in Ren-2 transgenic rats, suggesting a relationship between the enhanced angiotensinergic drive and central cardiovascular and vasopressin responses.

Topics: Analysis of Variance; Angiotensin II; Animals; Animals, Genetically Modified; Blood Pressure; Cerebral Ventricles; Heart Rate; Heterozygote; Hypertension; Injections, Intraventricular; Male; Rats; Rats, Sprague-Dawley; Saline Solution, Hypertonic; Vasopressins

It has been reported that intracerebroventricularly injected antisense oligonucleotide to angiotensinogen reduces arterial pressure in spontaneously hypertensive rats (SHR), but the mechanism and the sites of action remain unclear. In the present study, we examined whether injection of antisense oligonucleotide to angiotensinogen into the paraventricular hypothalamic nucleus (PVN) would influence arterial pressure and vasopressin release. For this purpose, 12-week-old male SHR were cannulated into the bilateral PVN. One week later, we injected antisense or sense oligonucleotide to angiotensinogen into the bilateral PVN (0.2 nmol/200 nl each side). After 24 h, we directly monitored arterial pressure, and then took blood samples to measure plasma vasopressin, catecholamines and renin activity. Mean arterial pressure did not change in either group (from 144+/-3 to 154+/-4 mmHg for the antisense oligonucleotide group, n=11; from 147+/-4 to 156+/-3 mmHg for the sense oligonucleotide group, n=11). Antisense oligonucleotide attenuated vasopressin release compared with sense oligonucleotide (1.30+/-0.28 vs. 3.29+/-0.60 pg/ml, respectively, P<0.01). Plasma catecholamines also decreased in the antisense oligonucleotide group compared with the sense oligonucleotide group. However, the plasma renin activity did not differ between the groups. In the additional experiment, we examined the neurohormonal and cardiovascular effects of intracerebroventricularly injected antisense oligonucleotide to angiotensinogen in SHR. Mean arterial pressure, plasma vasopressin and plasma norepinephrine were significantly lower in the antisense oligonucleotide group than in the sense oligonucleotide group. These results suggest that angiotensinogen in PVN plays important roles in vasopressin release and sympathetic nerve activity, but may not contribute to the maintenance of arterial pressure in SHR.

Topics: Angiotensinogen; Animals; Hypertension; Injections, Intraventricular; Male; Oligonucleotides; Oligonucleotides, Antisense; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Secretory Rate; Vasopressins

This study assessed whether the angiotensin-II (Ang II)-induced contractile responsiveness of resistance arteries is altered during the development of hypertension in spontaneously hypertensive rats (SHR). Structural parameters and Ang II-stimulated contraction were determined in small mesenteric arteries from 6-week-old (phase of developing hypertension) and 21-week-old SHR (phase of established hypertension), compared with age-matched Wistar-Kyoto rats (WKY). To ascertain whether effects were specific for Ang II, contractile responses to another vasoactive agonist, vasopressin (AVP), were also determined. Systolic blood pressure was measured in conscious rats by the tail-cuff method. Segments of third-order mesenteric arteries (approximately 200 microm in diameter and 2 mm in length) were mounted in a pressurized system with the intraluminal pressure maintained at 45 mm Hg. Blood pressure was significantly increased in SHR (P < .001) and was higher in adult than in young SHR (P < .001). Ang II dose-dependently increased contraction, with responses significantly greater (P < .05) in SHR than in age-matched WKY. SHR, in the early phase of hypertension, exhibited significantly augmented contractile responses (Emax = 70 +/- 5%), compared with SHR with established hypertension (Emax = 33 +/- 5%). These effects were not generalized, as responses to AVP were not significantly different between young and adult SHR. Functional Ang II-elicited alterations were associated with structural modifications: 6-week-old SHR had smaller media to lumen ratio compared with 21-week-old SHR (8.1% +/- 0.17% v 10.6% +/- 0.20%, P < .01). In young SHR vessels the media cross-sectional area was unchanged relative to age-matched WKY rats, suggesting eutrophic remodeling (remodeling index 101.4% v 93.3% young v adult), whereas the cross-sectional area of adult vessels was increased in comparison to WKY rats, suggesting mild hypertrophic remodeling (growth index -1.0% v 15.2%, young v adult). In conclusion, the present study demonstrates that in SHR with early hypertension and slight medial thickening, Ang II-mediated vascular contractile responsiveness is significantly augmented compared with SHR with established hypertension and more severe vascular structural changes. These findings indicate attenuation, as hypertension progresses, of the initially enhanced vascular reactivity to Ang II that is present during the development of hypertension in SHR.

Topics: Angiotensin II; Animals; Blood Pressure; Follow-Up Studies; Hypertension; Male; Mesenteric Arteries; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vascular Resistance; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Hypertension is associated with structural and mechanical abnormalities of resistance arteries. We have recently reported that vasopressin may be involved in the blood pressure elevation and remodeling of resistance arteries in deoxycorticosterone acetate (DOCA)-salt hypertension, perhaps by modulating vascular endothelin-1 expression. We tested this hypothesis further by examining DOCA-salt hypertension in homozygous vasopressin-deficient Brattleboro (BB) rats in comparison with Long-Evans (LE; control) rats. Mesenteric resistance arteries (lumen <300 microm) were studied on pressurized myographs. After 5 weeks, systolic blood pressure was greater in LE DOCA-salt-treated rats (189+/-5 mm Hg) compared with uniephrectomized (UNx) LE control rats (117+/-4 mm Hg; P<0.01). The increase in blood pressure induced by DOCA-salt treatment was attenuated in vasopressin-deficient rats, such that BB DOCA-salt-treated rats exhibited only a slight elevation of blood pressure (134+/-6 mm Hg) compared with BB-UNx rats (111+/-4 mm Hg; P<0.05). Resistance arteries in LE DOCA-salt-treated rats had a smaller lumen diameter and a larger media width, media cross-sectional area, and media-lumen ratio compared with LE-UNx rats. Isobaric stiffness was unaltered in resistance arteries from LE DOCA-salt-treated rats, despite stiffening of the arterial wall components as indicated by a significant increase in the slope of the media stress-incremental elastic modulus relationship. DOCA-salt treatment in the absence of endogenous vasopressin, ie, in homozygous di/di BB rats, failed to alter vascular structure or wall component stiffness and resulted in a lesser degree of blood pressure elevation. Reverse transcription-polymerase chain reaction analysis revealed that DOCA-salt treatment enhanced endothelin gene expression in LE rats but failed to do so in BB rats. These data indicate that vasopressin plays a critical role in modulating vascular structure and mechanics, as well as blood pressure, in DOCA-salt-induced hypertension. Moreover, these effects of vasopressin are in part mediated by enhancement of endothelin expression.

Topics: Animals; Arteries; Blood Pressure; Desoxycorticosterone; Endothelin-1; Hypertension; Male; Rats; Rats, Long-Evans; Vascular Resistance; Vasopressins

Ultrafiltration during haemodialysis (HD) may be the cause of blood pressure (BP) decline due to reduction of blood volume. In some patients, however, BP does not decrease or even rises during HD. The aim of the study was to answer the question: do uraemic hypertensive patients, showing a decline of mean blood pressure (MAP) during HD session (group A) differ from those showing a stable MAP during HD session (group B) with respect to hormonal profile of aldosterone (ALD), vasopressin (AVP), atrial natriuretic peptide (ANP), endothelin-1,2 (ET-1,2), blood nitric oxide (NO) and plasma renin activity (PRA). A total of 39 haemodialysed, hypertensive patients (17 female, 22 men) were studied. 24 patients (group A) showed a MAP decline of 10 mm Hg or more, while 15 patients (group B) showed MAP changes of less than +/- 10 mm Hg during HD session. PRA, ALD, AVP, ANP, ET-1,2, NO concentration were assessed in blood samples withdrawn from the arterial blood line before HD and after 60, 120, 180 and 240 minutes of HD session. Plasma ET-1,2 and blood NO concentration were also assessed after 30 minutes of HD. BV was continuously monitored with a Crit-Line equipment, BP was measured before and every 30 minutes on HD. Before HD session both examined groups showed similar baseline plasma levels of ALD, AVP, ANP, ET-1,2, NO, PRA and MAP. A 4-hours HD induced a significant increase in plasma ALD and AVP concentrations and a significant decline in ANP level in both groups of patients. In group A, PRA and blood NO concentration increased significantly, while plasma ET-1,2, level did not change during HD. In group B, no significant changes in PRA and blood NO level were noticed, while plasma ET-1,2 rose markedly. In addition in group B, a significant positive correlation was found between MAP and plasma ET-1,2 level changes, but a significant negative correlation between MAP and blood NO level changes.. Patients with a decline of MAP over 10 mm Hg during HD differ from those with a stable MAP by a different response of plasma ET and blood NO to HD induced volume changes.

Topics: Aldosterone; Atrial Natriuretic Factor; Blood Volume; Female; Humans; Hypertension; Male; Nitric Oxide; Renal Dialysis; Severity of Illness Index; Uremia; Vasopressins

The (mRen-2)27 transgenic rat (Tg+), a hypertensive model dependent on increased expression of the renin angiotensin system, was used to explore the role of angiotensin AT2 receptors in the control of cardiovascular and renal excretory function. Experiments tested the effect of blockade of AT2 receptors on basal blood pressure and the pressor, renal excretory, and vasopressin (VP) responses to intravenous hypertonic saline (HS). Chronically catheterized male Tg+ and normotensive Sprague-Dawley rats (Tg-) were housed in metabolic cages. PD123319 (AT2 antagonist) or 0.9% NaCl was given by intravenous bolus (3 mg/kg) followed by infusion (50 microg/kg/ min). Blockade of AT2 receptors both in Tg+ and Tg- rats produced no change in basal mean arterial pressure (MAP). The pressor response to intravenous HS (10% NaCl; 325 microL/100 g body weight) was significantly greater in Tg+ than in Tg- rats. PD123319 did not affect the peak rise in MAP but extended the time course of the response only in Tg+ rats. MAP was increased 39+/-4 and 36+/-3 mm Hg in Tg+ rats with and without the antagonist as compared to 20+/-2 and 24+/-2 mm Hg in Tg- rats. In the antagonist-treated Tg+ rats, MAP remained elevated for 60 min as compared to 5 min for Tg+ control or Tg- control or antagonist-treated rats. Hypertonic saline caused similar increases in plasma Na, VP, and in the natriuretic and diuretic responses in both Tg+ and Tg- rats, with no effect of antagonist treatment. These results demonstrate that Tg+ rats are sensitive to the effects of peripheral osmotic stimulation showing an increased pressor response, not attributed to greater secretion of VP or diminished natriuresis. These data also suggest that angiotensin AT2 receptors play a depressor role in the sodium-induced pressor response in this model.

Topics: Angiotensin Receptor Antagonists; Animals; Animals, Genetically Modified; Blood Pressure; Diuresis; Hypertension; Imidazoles; Infusions, Intravenous; Male; Natriuresis; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin; Reference Values; Renin; Saline Solution, Hypertonic; Vasopressins

Vasopressin (VP) is thought to play an important role in the pressor and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the H-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease.

Topics: Animals; Blood Chemical Analysis; Blood Pressure; Cell Division; Heart Rate; Hypertension; Kidney Glomerulus; Microscopy, Fluorescence; Organ Size; Platelet-Derived Growth Factor; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-sis; Rats; Rats, Inbred SHR; RNA, Messenger; Transforming Growth Factor beta; Vasopressins

A 66-year-old hypertensive male with acute intracerebral hemorrhage developed acute hyponatremic coma 3 days after the addition of enalapril and a combination of amiloride and a thiazide diuretic to his hypotensive regimen. The patient recovered consciousness and serum sodium normalized 2 days after fluid restriction and withdrawal of both medications. Three weeks later, upon inadvertent reinstitution of enalapril and indapamide, severe hyponatremic encephalopathy promptly recurred; recovery was again rapid following fluid restriction and withdrawal of both medications. This temporal relationship establishes the thiazide diuretic or the angiotensin converting enzyme inhibitor or both as the cause of the profound symptomatic hyponatremia in this patient. Results of simultaneous serum and urine osmolality assays on several occasions were consistent with a decrease in free water clearance, a result of either increased antidiuretic hormone (ADH) secretion or potentiation of its peripheral action, and thiazide-induced natriuresis. The use of a thiazide diuretic in the presence of either of these aberrations of ADH homeostasis most likely explains the profound and rapid development of hyponatremia. Drug-induced disturbances in serum osmolality are a potentially reversible cause of deterioration of the mental state in a patient with an acute cerebrovascular accident.

Topics: Aged; Amiloride; Benzothiadiazines; Central Nervous System; Cerebral Hemorrhage; Coma; Diuretics; Enalapril; Humans; Hypertension; Hyponatremia; Indapamide; Male; Osmolar Concentration; Sodium; Sodium Chloride Symporter Inhibitors; Vasopressins; Water

1. Vasopressin V1a and V2 receptors are differentially regulated in deoxycorticosterone acetate-salt hypertension. This paper investigated whether the changes were due to transcription changes in receptor mRNA assessed by in situ hybridization histochemistry (liver V1a receptor) and by reverse transcription-polymerase chain reaction (kidney V1a and V2 receptor). 2. Systolic blood pressure and plasma vasopressin levels were significantly elevated in deoxycorticosterone acetate-salt rats (n = 24) compared with water-control (n = 28) and salt-control rats (n = 28) (P < 0.001). Plasma sodium was elevated in deoxycorticosterone acetate-salt rats compared with both control groups (P < 0.01) and plasma osmolality was elevated in deoxycorticosterone acetate-salt rats compared with water-control rats (P < 0.05). 3. Binding kinetic studies demonstrated downregulation of liver V1a and kidney V2 receptors in deoxycorticosterone acetate-salt rats compared with water-control and salt-control rats (P < 0.05). This was not associated with any change in liver V1a receptor mRNA (P = 0.95), or in kidney V1a (P = 0.79) or V2 receptor mRNA (P = 0.96). 4. In deoxycorticosterone acetate-salt hypertension, downregulation of liver V1a and kidney V2 receptors occurs in the setting of stable vasopressin gene transcription. These results suggest that changes in receptor processing may be responsible for the differential regulation of vasopressin receptors that occurs in deoxycorticosterone acetate-salt hypertension.

Topics: Animals; Autoradiography; Desoxycorticosterone; Hypertension; In Situ Hybridization; Kidney; Liver; Male; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; RNA, Messenger; Sodium; Sodium Chloride; Transcription, Genetic; Vasopressins

Conflicting evidence exists on the possible impairment of tonic nitric oxide (NO) mediated vasodilation as a causative factor in the genesis of human as well as experimental hypertension. We evaluated the tonic NO-dependent vasodilation from the pressor response to NO synthesis inhibition by NG-monomethyl-L-arginine (L-NMMA) in 9 conscious, chronically instrumented spontaneously hypertensive rats (SHR) at 12 weeks of age, ie, during the early established hypertensive stage. Nine age-matched Wistar-Kyoto rats (WKY) were used as controls. The pressor responses to L-NMMA (100 mg . kg-1 IV bolus plus 1.5 mg . kg-1 . min-1 infusion for 60 minutes) as well as to non NO-dependent pressor stimuli, namely, vasopressin (2, 4, and 8 ng . kg-1) and phenylephrine (0.5, 1, and 2 microg . kg-1) given as IV boluses, were assessed both under control conditions and during suppression of autonomic reflexes by hexamethonium (30 mg . kg-1 IV bolus+1.5 mg . kg-1 . min-1 infusion). Rather than being reduced, the pressor responses to L-NMMA were 39% and 71% larger in the control and areflexic conditions, respectively, than those observed in WKY (both P<0.01). A similar pattern was observed for the pressor responses to vasopressin (+37% and +68% in the control and areflexic conditions, respectively; both P<0.01) and phenylephrine, (+20% and +52%; both P<0.05). Additional groups of 6-week-old prehypertensive SHR (n=11) and age-matched WKY (n=11) were subjected to an identical protocol: in these animals, the pressor responses to L-NMMA were similar in each strain, as were the pressor responses to vasopressin and phenylephrine in both control and areflexic conditions. In conclusion, our observations indicate that during the developmental phase of hypertension in the SHR model, namely, during the prehypertensive as well as the early established hypertensive stage, NO-dependent vasodilation is preserved (if not enhanced) so that a putative impairment of this function provides no significant pathogenic contribution to the onset of hypertension in this experimental model.

Topics: Aging; Animals; Antihypertensive Agents; Blood Pressure; Drug Interactions; Enzyme Inhibitors; Hexamethonium; Hypertension; Infusions, Intravenous; Nitric Oxide; omega-N-Methylarginine; Pressoreceptors; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Species Specificity; Vasoconstrictor Agents; Vasodilation; Vasopressins

We have reported that lovastatin attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The fall in arterial pressure is associated with an elevation in renal medullary blood flow, normalization of the pressure-natriuresis relationship, and diminished hypertrophy of renal arterioles. However, the mechanism by which lovastatin alters renal vascular tone is unknown. The present study examined the effects of lovastatin on renal vascular tone and the expression of G proteins. Four-week-old SHR were chronically treated with lovastatin (20 mg/kg/day) or vehicle by gavage for 4 weeks. At the end of the study, mean arterial pressure averaged 131 +/- 4 (n = 5) and 160 +/- 4 mm Hg (n = 6) in lovastatin- and vehicle-treated SHR, respectively. Renal arterioles isolated from lovastatin-treated SHR were significantly less responsive to norepinephrine and vasopressin than those obtained from vehicle-treated rats (ED50: 5.0 v 1.8 x 10(-7) mol/L for norepinephrine, and 8.0 v 5.2 x 10(-10) mol/L for vasopressin). The fall in renal vascular reactivity in lovastatin-treated SHR was associated with reduced levels of ras and rho proteins in renal arterioles, whereas the expressions of heterotrimeric G proteins (Gs Gq, Gi) were similar in renal arterioles from vehicle- and lovastatin-treated SHR. Overnight culture of renal arterioles with media containing lovastatin also diminished the expression of ras and rho proteins and the response to vasoconstrictors. These findings indicate that lovastatin diminishes the response to vasoconstrictors and the expression of small G proteins in the renal vasculature of SHR and suggest that a fall in the levels of ras and rho proteins in these vessels may contribute to the antihypertensive effects of lovastatin.

Topics: Animals; Arterioles; Blood Pressure; GTP-Binding Proteins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Lovastatin; Norepinephrine; Rats; Rats, Inbred SHR; Renal Circulation; Vasoconstriction; Vasoconstrictor Agents; Vasomotor System; Vasopressins

Renin transgenic hypertensive rats [TGR(mRen2)27] have increased contents of angiotensin II and arginine vasopressin (AVP) in the cardiovascular brain regions. The aim of the present study was to evaluate the effects of centrally released AVP on the regulation of baseline blood pressure in TGR(mRen2)27 rats and to determine the interaction between AVP and angiotensin II in the central control of blood pressure in this model of hypertension.. Three basic series of experiments were performed on 20 TGR(mRen2)27 and 20 Hannover Sprague-Dawley conscious rats, chronically instrumented with lateral cerebral ventricle (LCV) cannulae and femoral artery catheters. In series 1, blood pressure and heart rate were recorded during an LCV infusion of artificial cerebrospinal fluid before and after LCV administration of angiotensin II. In series 2, the effects of an LCV administration of angiotensin 11 (100 ng) on mean arterial pressure and the heart rate were determined during LCV infusion of a selective AVP receptor (V1) antagonist [1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine vasopressin (MeCAAVP) and d(CH2)5[Tyr(Me)2,Ala-NH2(9)]AVP] or a selective angiotensin II type 1 (AT1) receptor antagonist (losartan) or both. In series 3, mean arterial pressure and the heart rate were determined after an LCV injection of either AVP (10 ng) or AVP together with angiotensin II.. The LCV infusions of antagonists to V1 and AT1 receptors caused significant comparable decreases in baseline MAP in TGR(mRen2)27 but not in Sprague-Dawley rats. Angiotensin II elicited significant pressor responses, both in TGR(mRen2)27 and in Sprague-Dawley rats. Blockade of V1 receptors significantly reduced the duration and the maximum amplitude of the central pressor response to angiotensin II in TGR(mRen2)27 rats, whereas in Sprague-Dawley rats the maximum pressor effect was not significantly altered. In both strains, the pressor response to angiotensin II was abolished by blockade of AT1 receptors.. The results indicate that the elevated blood pressure in TGR(mRen2)27 rats is partly caused by increased function of the brain angiotensinergic AT1 and vasopressinergic V1 systems. Centrally released AVP is involved in mediation of the pressor effect exerted by centrally applied angiotensin II in TGR(mRen2)27 rats.

Topics: Angiotensin II; Animals; Animals, Genetically Modified; Antihypertensive Agents; Arginine Vasopressin; Blood Pressure; Cerebral Ventricles; Cerebrospinal Fluid; Hormone Antagonists; Hypertension; Losartan; Male; Rats; Rats, Sprague-Dawley; Renin; Vasopressins

Indices of carbohydrate and lipid metabolism were investigated in male New Zealand genetically hypertensive and normotensive rats. Cross-breeding of male rats of these strains with female Brattleboro diabetes insipidus rats also provided the opportunity to examine the metabolic impact of vasopressin and its deficiency in hypertensive and normotensive rats. Hypertensive and normotensive rats, with or without diabetes insipidus, were fasted for 24 h, exsanguinated and their blood/plasma analysed for various indices of carbohydrate and lipid metabolism. Whilst each group of rats maintained fasted normoglycemia, hypertensive rats, with or without vasopressin-deficiency, were hypoinsulinaemic relative to normotensive counterparts. Moreover, hypertensive or normotensive vasopressin-deficient rats were hypoinsulinaemic relative to vasopressin-replete counterparts. In vasopressin-replete rats, the apparently improved insulin sensitivity in hypertension was associated with significant falls in plasma glucagon, triglycerides and total cholesterol. Finally, normotensive vasopressin-deficient rats were hypoglucagonaemic relative to the vasopressin-replete group. These data demonstrate that independent of vasopressin status, hypertension in the New Zealand strain and the diabetes insipidus hybrid was associated with improved insulin sensitivity. However, endogenous vasopressin exercises an influential role in carbohydrate and lipid metabolism in normotensive rats.

Topics: Animals; Blood Glucose; Cholesterol; Crosses, Genetic; Diabetes Insipidus; Female; Glucagon; Hypertension; Insulin; Lipids; Male; Rats; Rats, Brattleboro; Triglycerides; Vasopressins

It has been shown that vasopressin receptors are upregulated in the brain and that the central vasopressin pathway is involved in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. However, it is unclear whether central vasopressin, in itself, is essential for this type of hypertension. To clarify this issue, the effect of centrally administered vasopressin on the development of DOCA-salt hypertension was studied in homozygous Brattleboro rats which genetically lack vasopressin. In homozygous Brattleboro rats, treatment with intracerebroventricular infusion of vasopressin (1 ng/h) alone or DOCA-salt (weekly subcutaneous injection of 30 mg/kg deoxycorticosterone acetate and 0.3% NaCl to drink) alone had no effect on systolic blood pressure (SBP). On the other hand, hypertension was partially restored in homozygous Brattleboro rats treated with intracerebroventricular infusion of vasopressin and DOCA-salt (SBP: 175 +/- 4 mmHg), although the magnitude of elevation of SBP was one-third of that in Long Evans rats treated with DOCA-salt (278 +/- 15 mmHg). These hypertensive homozygous Brattleboro rats showed an increase in fluid intake and urinary sodium excretion, as observed in DOCA-salt hypertensive Long Evans rats. These results suggest that central vasopressin is required for the complete development of DOCA-salt hypertension and the mechanism is, in part, due to enhanced sodium intake through the additive effect of central vasopressin and DOCA-salt.

Topics: Animals; Blood Pressure; Body Weight; Desoxycorticosterone; Diabetes Insipidus; Disease Models, Animal; Hypertension; Male; Rats; Vasopressins

Regular administration of recombinant erythropoietin (EPO) in patients with chronic renal failure (CRF) is frequently complicated by a rise in arterial blood pressure. Clinical studies intended to discern the possible role of endothelin (ET) in the pathogenesis of EPO-induced hypertension have produced contradictory results. Given the limitations of the clinical studies, this placebo-controlled study was carried out in CRF (5/6 nephrectomized) rats treated with either EPO, 150 U/kg intraperitoneally, or the vehicle alone twice weekly for 6 wk. Plasma ET was measured at baseline, and weeks 2, 4, and 6. In addition, plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were determined at the conclusion of the study period. As expected, blood pressure rose markedly after 1 wk of EPO therapy as compared with the placebo therapy. However, there was no significant difference in plasma ET levels between the EPO- and placebo-treated groups during the study period. Likewise, EPO therapy had no effect on plasma ANP level but depressed plasma AVP concentration. Thus, this placebo-controlled animal study revealed that EPO therapy markedly raised arterial blood pressure but had no effect on plasma ET in the CRF rats. This observation suggests that EPO-induced hypertension in this model is not mediated by an increased circulating ET level. However, the possible effect, if any, of EPO on local vascular tissue ET level is uncertain and awaits further investigation.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Endothelins; Erythropoietin; Hypertension; Longitudinal Studies; Male; Rats; Rats, Sprague-Dawley; Vasopressins

Recently, we demonstrated that elevated blood pressure activates mitogen-activated protein (MAP) kinases in rat aorta. Here we provide evidence that the vascular response to acute hypertension also includes induction of MAP kinase phosphatase-1 (MKP-1), which has been shown to function in the dephosphorylation and inactivation of MAP kinases. Restraint or immobilization stress, which leads to a rapid rise in blood pressure, resulted in a rapid and transient induction of MKP-1 mRNA followed by elevated MKP-1 protein expression in rat aorta. That the induction of MKP-1 by restraint was due to the rise in blood pressure was supported by the finding that several different hypertensive agents (phenylephrine, vasopressin, and angiotensin II) were likewise capable of eliciting the response, and sodium nitroprusside, a nonspecific vasodilator agent that prevented the acute rise in blood pressure in response to the hypertensive agents, abrogated MKP-1 mRNA induction. The in vivo effects could not be mimicked by treatment of cultured aortic smooth muscle cells with similar doses of the hypertensive agents. These findings support a role for MKP-1 in the in vivo regulation of MAP kinase activity during hemodynamic stress.

Topics: Acute Disease; Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Blotting, Western; Cardiovascular System; Cells, Cultured; Data Interpretation, Statistical; Enzyme Activation; Gene Expression Regulation, Enzymologic; Hypertension; Male; Mitogens; Muscle, Smooth, Vascular; Nitroprusside; Phenylephrine; Phosphoprotein Phosphatases; Protein Kinases; Protein Phosphatase 1; Rats; Rats, Wistar; Restraint, Physical; RNA; Stress, Physiological; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

It has been reported that acupuncture can decrease blood pressure in patients with hypertension, possibly by an endocrine mechanism. The aim of the present study was to investigate the effects of acupuncture on arterial blood pressure and the secretion of renin, vasopressin and cortisol in hypertensive patients. Acupuncture was performed in fifty untreated essential hypertensive patients resting in the supine position. Thirty min after acupuncture there were decreases in systolic pressure from 169 +/- 2 to 151 +/- 2 mm Hg, diastolic pressure from 107 +/- 1 to 96 +/- 1 mm Hg, and heart rate from 77 +/- 2 to 72 +/- 2 bpm (P < 0.01). Plasma renin activity decreased from 1.7 +/- 0.4 to 1.1 +/- 0.2 ng/ml/2h (P < 0.01), but there were no significant changes in plasma vasopressin or cortisol concentrations. These results confirm that acupuncture decreases blood pressure in hypertensive patients, and suggest that the decrease results, at least in part, from a decrease in renin secretion.

Topics: Acupuncture Therapy; Adolescent; Adult; Blood Pressure; Female; Heart Rate; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Radioimmunoassay; Renin; Supine Position; Vasopressins

Changes in blood pressure, cardiac output, and total peripheral conductance evoked by intravenous infusions of [Arg8]-vasopressin (vasopressin) were recorded before and after pretreatment with bosentan, a non-selective endothelin antagonist, in conscious unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The presser effects of vasopressin were exaggerated in SHR compared to WKY. Pretreatment with bosentan failed to change hemodynamic responses of WKY to vasopressin, but it blunted the increases in blood pressure and the decreases in conductance evoked by vasopressin in SHR. In contrast, bosentan failed to change cardiac output responses of SHR to vasopressin. Except at the highest dose of vasopressin, bosentan abolished the exaggerated pressor responsiveness of the SHR to vasopressin. The results suggest that endothelin contributes to the exaggerated pressor responsiveness of SHR to vasopressin, and that this effect is exerted at the level of the resistance vessels and not on factors that regulate cardiac output.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Bosentan; Cardiac Output; Dose-Response Relationship, Drug; Endothelin-1; Heart Rate; Hemodynamics; Hypertension; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sulfonamides; Vasoconstrictor Agents; Vasopressins

1. Male, vasopressin-deficient, normotensive (DI/N) and hypertensive (DI/H) rats were chronically instrumented (all surgery under sodium methohexitone anaesthesia) to allow assessment of resting haemodynamic status and responses to antagonism of AT1-receptors (Experiment 1), ET(A-) and ET(B-) receptors (Experiment 2) or adrenoceptors (Experiment 3). 2. Before any treatment, mean arterial blood pressure (MAP) was higher, and hindquarters vascular conductance was consistently lower in all groups of DI/H rats than in DI/N rats. 3. In Experiment 1, losartan (10 mg kg-1 i.v.), an AT1-receptor antagonist, was given 5 h after s.c. injection of saline, (DI/N, n = 8; DI/H, n = 8) or hyperoncotic polyethylene glycol, (DI/N, n = 9; DI/H, n = 9) to induce isosmotic hypovolaemia. In the volume-replete state, losartan caused similar small falls in MAP in the two groups (maximum delta MAP; DI/N, -9 +/- 2; DI/H, -15 +/- 5 mmHg), but the mesenteric and hindquarters vasodilatations were greater in DI/N rats. In the volume-depleted state the effects of losartan were augmented (delta MAP; DI/N, -32 +/- 3; DI/H. -31 +/- 3 mmHg), but its vasodilator effects were still greater in DI/N than in DI/H rats. 4. In Experiment 2, infusion of the ET(A-)ET(B-)receptor antagonist, SB 209670 (600 micrograms kg-1 h-1; DI/N, n = 8; DI/H, n = 9), had haemodynamic effects that were not different from those during saline infusion in DI/N (n = 7) and DI/H rats (n = 8). 5. In Experiment 3, sequential administration of the beta 2-adrenoceptor antagonist, ICI 118551 (0.2 mg kg-1 bolus, 0.1 mg kg-1 h-1 infusion), the alpha 2-adrenoceptor antagonist, idazoxan (0.75 mg kg-1 bolus, 1 mg kg-1 h-1 infusion), and losartan (10 mg kg-1 bolus) had only slight haemodynamic effects in DI/N (n = 8) and DI/H (n = 9) rats. Subsequent administration of the alpha 1-adrenoceptor antagonist, prazosin (0.5 mg kg-1 bolus, 0.8 mg kg-1 h-1 infusion) caused marked hypotension, although MAP was still higher in DI/H (95 +/- 4 mmHg) than in DI/N (75 +/- 4 mmHg) rats. However, in this circumstance there were no significant differences between renal, or mesenteric, or hindquarters vascular conductances in the two groups. 6. The results indicate that the hypertension and hindquarters vasoconstriction in DI/H rats is not dependent on AII or endothelin. Moreover, the relative elevation in MAP in DI/H persists in the presence of antagonism of beta 2, alpha 2- and alpha 1-adrenoceptors, in spite of no significant difference in reg

Topics: Adrenergic Antagonists; Angiotensin II; Animals; Biphenyl Compounds; Endothelins; Hemodynamics; Hypertension; Imidazoles; Indans; Losartan; Male; Rats; Sodium Chloride; Tetrazoles; Vasopressins

1. The full therapeutic potential of the main immunosuppressive drug, cyclosporin A (CsA), is limited because of its side effects, namely nephrotoxicity and hypertension. Several lines of evidence suggest that the origin of both side effects could be CsA-induced vasoconstriction. However, the underlying molecular mechanisms are not well understood. 2. Diameter measurements of rat isolated mesenteric arteries showed an increase in noradrenaline- and [Arg]8vasopressin-induced vasoconstriction when arteries were pretreated with CsA. 3. Measurements in cultured vascular smooth muscle cells (VSMC) of either cytosolic calcium concentration or of 45Ca2+ efflux showed that CsA potentiated the calcium influx to several vasoconstrictor hormones: [Arg]8vasopressin, angiotensin II, endothelin-1 and 5-hydroxytryptamine. On the other hand, 45Ca2+ efflux in response to thapsigargin, which depletes calcium from intracellular pools, was not potentiated by CsA. 45Ca2+ uptake was not altered by CsA or by any of the analogues tested. 4. Time-course studies in cultured VSMC showed that maximal CsA-induced Ca2+ potentiation occurred after ca. 20 h and this effect was reversed over approximately the next 20 h. 5. To investigate the possible role played by the known intracellular targets of CsA, namely cyclophilin and calcineurin, CsA derivatives with variable potencies with respect to their immunosuppressive activity, were tested on the calcium influx to [Arg]8vasopressin. Derivatives devoid of immunosuppressive activity (cyclosporin H, PSC-833) potentiated calcium signalling, while the potent immunosuppressant, FK520, a close derivative of FK506, and MeVal4CsA, an antagonist of the immunosuppressive effect of CsA did not. The latter compound was unable to reverse the calcium potentiating effect of CsA. 6. Our results show that CsA increases the calcium influx to vasoconstrictor hormones in smooth muscle cells, which presumably increases vasoconstriction. Loading of the intracellular calcium pools appears not to be involved. Experiments with derivatives of CsA and FK520 suggest that interactions with cyclophilins and calcineurin are not the mechanism involved. This indicates, for the first time, that the immunosuppressive activity can be dissociated from the calcium potentiating effect of CsA in vascular smooth muscle.

Topics: Adrenergic alpha-Agonists; Amino Acid Isomerases; Animals; Calcineurin; Calcium; Calmodulin-Binding Proteins; Carrier Proteins; Cyclosporine; Dose-Response Relationship, Drug; Enzyme Inhibitors; Hypertension; Immunosuppressive Agents; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Norepinephrine; Peptidylprolyl Isomerase; Phosphoprotein Phosphatases; Rats; Rats, Inbred WKY; Thapsigargin; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Propranolol, a non-selective beta-blocker, is used for treatment of portal hypertension as it is believed to diminish splanchnic blood flow both by reducing cardiac output (beta(1)-blockade) and by increasing splanchnic arteriolar resistance (beta(2)-blockade). However, possible vasodilatory properties of propranolol at higher concentrations may counteract splanchnic vasoconstriction. Nadolol, another nonselective beta-blocker, has also been suggested for treatment of portal hypertension. The aim of the present study was to investigate the effects of various concentrations of propranolol and nadolol on vascular resistance in isolated perfused mesenteric arterial beds from normal and portal hypertensive rats. At concentrations of 10(-7) mol L-1 to 10(-6) mol L-1 neither propranolol nor nadolol changed pressor responses to noradrenaline in normal rats. However, nadolol 10(-5) mol L-1 significantly increased, whereas propranolol 10(-5) mol L-1 reduced, noradrenaline-induced vasoconstriction both in normal and in portal hypertensive rats. This unexpected vasodilatory effect of propranolol at high concentrations was present in preparations stimulated by both noradrenaline and methoxamine but not vasopressin and thus may be due to competitive alpha-receptor blockade. In contrast, nadolol lacked this effect and produced splanchnic arteriolar vasoconstriction at high concentrations also.

Topics: Adrenergic beta-Antagonists; Animals; Antihypertensive Agents; Hypertension; Male; Mesentery; Methoxamine; Nadolol; Norepinephrine; Perfusion; Propranolol; Rats; Rats, Sprague-Dawley; Vascular Resistance; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

To investigate the effects of vasopressin and endothelin-1 on the intracellular free calcium concentration ([Ca2+]i) and on contractile responses in endothelium-denuded resistance vessels of prehypertensive (5-week-old) and adult hypertensive (17-week-old) spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats.. Segments (2 mm long) of third-order branches of small mesenteric arteries were mounted in a perfusion myograph and maintained at 60 mmHg pressure. Endothelium was removed by intraluminal passage of air. The vessel [Ca2+]i was measured by fura-2 fluorescence and contraction was determined using a video imaging system to record lumen diameter.. Lumen diameter was significantly smaller in 5-and 17-week-old SHR than it was in age-matched WKY rats (5 week-old SHR versus WKY rats: 178 +/- 4.0 versus 195 +/- 4.3 microns; 17-week-old SHR versus WKY rats: 168 +/- 7.0 versus 230 +/- 3.1 microns). The basal [Ca2+]i was significantly higher in 5- and 17-week-old SHR than it was in age-matched WKY rats. Infusions of vasopressin and endothelin-1 increased [Ca2+]i and contractile responses in a dose-dependent manner in all groups. The vasopressin-induced change in [Ca2+]i was significantly greater in 5- and 17-week-old SHR than in age-matched controls. The sensitivity of [Ca2+]i to vasopressin was increased in adult SHR compared with WKY rats (pD2 9.0 +/- 0.1 in SHR, 8.2 +/- 0.3 in WKY rats). Vasopressin-stimulated contractile responses were increased in adult SHR. The endothelin-1-induced change in [Ca2+]i did not differ between WKY rats and SHR. The contractility of vessels in response to endothelin-1 infusion was similar in age-matched groups.. Endothelin-1-induced changes in [Ca2+]i and contractile responses in small arteries are similar in age-matched WKY rats and SHR, whereas responses to vasopressin are significantly enhanced in SHR compared with WKY rats. Thus [Ca2+]i signalling for vasopressin is more active than is that for endothelin-1. Vasopressin but not endothelin-1 might play a role in the development of hypertension in SHR.

Topics: Animals; Blood Pressure; Calcium; Endothelin-1; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasoconstriction; Vasopressins

Orthotopic heart transplantation may interrupt key neural and humoral homeostatic mechanisms that normally adjust Na+ and fluid excretion to changes in intake. Such an interruption could lead to plasma volume expansion.. We measured plasma volume and fluid regulatory hormones under standardized conditions in 11 heart transplant recipients (58 +/- 7 years old; mean +/- standard deviation) 21 +/- 4 months after transplantation, in 6 liver transplant recipients (51 +/- 6 years old) 13 +/- 8 months after transplantation (cyclosporine control group), and in 7 normal healthy control subjects (61 +/- 9 years old). Administration of all diuretics and antihypertensive drugs was discontinued before the study. After 3 days during which subjects ate a constant diet containing 87 mEq of Na+ per 24 hours, plasma volume was measured by a modified Evans blue dye (T-1824) dilution technique. Renal creatinine clearance was measured and blood samples were drawn for determination of plasma levels of vasopressin, angiotensin II, aldosterone, atrial natriuretic peptide, and plasma renin activity.. Supine resting plasma renin activity, angiotensin II, and aldosterone (renin-angiotensin-aldosterone axis) and vasopressin levels were not different among the control, heart transplant, and liver transplant groups. However, there was a trend toward elevated angiotensin II (p < or = 0.08) and aldosterone (p < or = 0.08) levels in the heart transplant recipients. Atrial natriuretic peptide levels were significantly elevated two to threefold in the heart transplant recipients when compared with those in the two control groups. Blood volume, normalized for body weight (milliliters per kilogram), was significantly greater (14%) in the heart transplant recipients when compared with that in liver transplant recipients and normal healthy control subjects. Blood volume values did not differ (p > or = 0.05) between the two control groups.. Extracellular fluid volume expansion (+14%) occurs in clinically stable heart transplant recipients who become hypertensive. Although hyperactivity of the renin-angiotensin-aldosterone axis is not apparent during supine resting conditions, our data suggest that the renin-angiotensin-aldosterone system is not responsive to a hypervolemic stimulus and this is likely a consequence of chronic cardiac deafferentation. Thus, poor adaptation of the renin-angiotensin-aldosterone system to fluid retention may be partly responsible for the incidence and severity of posttransplantation hypertension in some heart transplant recipients.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Denervation; Electrolytes; Female; Heart; Heart Transplantation; Hemodynamics; Hormones; Humans; Hypertension; Liver Transplantation; Male; Middle Aged; Neurosecretory Systems; Plasma Volume; Vasopressins; Ventricular Function, Left

Central nervous system feedback loops centered on hypothalamic neurons control atrial natriuretic peptide (ANP). We evaluated the ANP response to arterial hypotension, isotonic blood volume expansion, and increase in plasma osmolality in 14 patients with multiple system atrophy (MSA). Seven of the patients were characterized by a lack of vasopressin response to hypotension (MSA type B), suggesting chronic sinoaortic denervation, and seven by a preserved response (MSA type A). Orthostatic hypotension decreased ANP in controls and type A patients, whereas ANP in type B was not affected. Isotonic saline infusion increased ANP and diuresis in controls and type A patients, whereas it did not affect ANP in type B. Osmotic load increased plasma osmolality and vasopressin in controls and MSA patients and ANP in controls and type A but not in type B patients. In MSA patients with altered afferent control of vasopressin, ANP secretion is not stimulated by blood volume expansion, osmotic load, or blood pressure, suggesting that afferent excitatory control plays a role in the release of ANP.

Topics: Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Brain Diseases; Diuresis; Female; Humans; Hypertension; Isotonic Solutions; Male; Middle Aged; Nerve Degeneration; Osmolar Concentration; Posture; Saline Solution, Hypertonic; Sodium Chloride; Vasopressins

To measure blood pressure (BP), plasma endothelin-1 (ET-1), atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone (ALDO) concentration, and plasma renin activity (PRA) in patients treated with a low-dose cyclosporin A (CyA).. An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP).. Out-patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital.. CyA was given to 25 patients with RA and to 10 patients with PPP.. RA patients were given CyA at a dose of 2.5 +/- 0.13 mg kg-1 body weight (BW) to 3.47 +/- 0.79 mg kg-1 BW (mean values +/- SD) at the start of the study and after 6 months, respectively, and the CyA dose was 2.67 +/- 0.13 mg kg-1 BW decreasing to 2.07 +/- 0.96 mg kg-1 (P < 0.001) after 4 months in PPP subjects.. Systolic (sBP) and diastolic blood pressure (dBP) increased from 127.8 +/- 13.6/79.7 +/- 8.4 mmHg to 140.0 +/- 19.8/83.8 +/- 9.7 mmHg during the study (P < 0.03). Plasma ET-1, ANP, ALDO and ADH concentration and PRA did not change during 4 to 6 months of CyA treatment. The plasma ANP concentration was constantly higher in CyA-treated RA patients (112 +/- 87 ng 1-1 to 118 +/- 78 ng 1-1) than in PPP patients (37.3 +/- 26 ng 1-1 to 47.7 +/- 39.9 ng 1-1; P < 0.02). The serum creatinine concentration remained within the normal range, but increased from baseline (76.7 +/- 11.9 mumol 1-1), to 90 +/- 15.4 mumol 1-1 (p < 0.001). The serum magnesium concentration decreased significantly (P < 0.005) after 6 months of CyA treatment in RA patients. No correlation was found between serum creatinine and plasma ET-1 concentration.. Increased blood pressure during CyA treatment was independent of circulating ET-1 levels. A low dose of CyA did not induce increased ET-1 synthesis as judged from plasma samples. The high plasma ANP level observed in RA patients could be due to fluid retention caused by concomitant treatment with non-steroid anti-inflammatory drugs. Fluid retention and decreased magnesium levels could also be involved in the development of hypertension in CyA-treated subjects.

Topics: Adult; Aldosterone; Arthritis, Rheumatoid; Atrial Natriuretic Factor; Blood Pressure; Cyclosporine; Endothelins; Female; Humans; Hypertension; Male; Middle Aged; Psoriasis; Renin; Vasopressins

Observations that angiotensin-(1-7) [ANG-(1-7)] may oppose the vasoconstrictor actions of angiotensin II (ANG II) prompted an investigation of the effects of the heptapeptide on the maintenance of elevated blood pressure in spontaneously hypertensive rats (SHR). ANG-(1-7) (24 micrograms.kg-1.h-1) was infused into the jugular vein of 13-wk-old SHR (n = 64), Wistar-Kyoto (WKY, n = 50), and Sprague-Dawley (SD, n = 18) rats for 2 wk, with the use of osmotic minipumps. Blood pressure, fluid and electrolyte balance, plasma vasopressin, and urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured at days 2, 7, and 12 of the infusion. In SHR, ANG-(1-7) caused a sustained and significant reduction in plasma vasopressin concentration that was associated with an increase in urinary prostaglandin E2 and 6-keto-PGF1 alpha excretion at day 2 after the commencement of the infusion. These changes were accompanied by diuresis and natriuresis during the first 3 days of infusion in SHR but not in WKY or SD rats. Direct measurements of arterial pressure confirmed the lowering effect of ANG-(1-7) on systolic pressure of SHR on day 2 of treatment with a restoration of the pressure by days 7 and 12. These findings, along with our previous demonstration that ANG-(1-7) is an active depressor peptide in the intact animal, suggest that ANG-(1-7) may play a significant role as a vasodepressor system opposing the hemodynamic actions of ANG II in this genetic form of experimental hypertension.

Topics: Angiotensin I; Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Diuresis; Heart Rate; Hypertension; Infusions, Intravenous; Male; Natriuresis; Peptide Fragments; Prostaglandins; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reference Values; Time Factors; Vasopressins

In this study we examined the structural and functional properties of mesenteric resistance arteries isolated from normotensive and hypertensive vasopressin-deficient rats. Hypertensive rats had a significantly higher mean arterial pressure (176 +/- 3 mm Hg) than normotensive controls (121 +/- 2 mm Hg). First- and second-order mesenteric resistance arteries were set up in a pressure myograph and pressurized to the mean arterial pressure of the rat from which they had been isolated. Vessels were fixed with glutaraldehyde, embedded in Araldite, sectioned, and examined histologically. First- and second-order mesenteric resistance arteries from hypertensive rats displayed a reduced internal diameter and increased media-to-lumen ratio compared with their normotensive controls. However, there was no evidence for an increased media content, indicating that the reduced internal diameter of hypertensive arteries was consequent to either remodeling of similar amounts of wall material or a reduced artery distensibility but not vascular growth. Pressurized arteries were also examined with respect to their responsiveness to the vasoconstrictors norepinephrine and arginine vasopressin and to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator papaverine. Both first- and second-order mesenteric arteries from hypertensive rats displayed enhanced sensitivity to norepinephrine compared with their normotensive controls. This effect was specific for norepinephrine, because responses to arginine vasopressin were similar in vessels isolated from normotensive and hypertensive rats. No evidence was found for an impaired endothelium-dependent vasodilatation in arteries from hypertensive rats. Indeed, in hypertensive vasopressin-deficient rats responses to acetylcholine were increased in first-order arteries compared with those from normotensive rats. Responses to papaverine were similar in arteries isolated from either normotensive or hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Hypertension; Male; Mesenteric Arteries; Microcirculation; Norepinephrine; Papaverine; Rats; Vascular Resistance; Vasopressins

To study the association between postural hypotension and (i) electrolyte levels and (ii) neurohumoral factors in elderly hypertensive patients using diuretics.. Cross-sectional study of patients and controls.. The subjects were gathered from senior citizen clubs or they were referred to the study by general practitioners. The subjects were examined on a geriatric ward in Turku City Hospital.. Seven subjects with postural hypotension and 13 controls.. Plasma electrolyte levels and neurohumoral response to head-up tilt.. There were significantly more hypokalaemic subjects in the postural hypotension group (5/7) than in the control group (1/13) (P < 0.01). The plasma potassium level was negatively correlated to plasma aldosterone (r = -0.57; P < 0.01) and renin activity (r = -0.69; P < 0.001). Subjects with postural hypotension had higher levels of noradrenaline, both supine (P < 0.05) and during tilt (P < 0.05). There were no significant differences in supine or tilt levels of plasma adrenaline, vasopressin, atrial natriuretic peptide, aldosterone and renin activity between the groups.. The results suggest that potassium depletion is associated with postural hypotension in elderly hypertensive patients using diuretics. However, it is unclear whether there is a causative link between potassium depletion and postural hypotension or whether they are both caused by some other factor, e.g. volume contraction.

Topics: Aged; Aged, 80 and over; Aldosterone; Atrial Natriuretic Factor; Case-Control Studies; Cross-Sectional Studies; Diuretics; Electrolytes; Epinephrine; Female; Humans; Hypertension; Hypotension, Orthostatic; Male; Neurotransmitter Agents; Potassium; Renin; Tilt-Table Test; Vasopressins

The present study was designed to clarify the potential of DQ-2511 (3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]carbamoyl]methyl] amino-N-methylbenzamide: ecabapide) as a gastroprokinetic agent in spontaneously hypertensive rats (SHR). The gastric emptying of SHR was clearly retarded relative to that of weight-matched normotensive Wistar-Kyoto (WKY) rats when evaluated by the acetaminophen (APAP) method with the semi-solid test meal. There was, however, no significant difference between both strains in gastric mucosal blood flow (GMBF) determined by means of a laser doppler flowmetry. A 2-week treatment of SHR with DQ-2511 (1 mg/kg, oral) stimulated gastric emptying without affecting body weight gain or indirect systolic blood pressure (SBP), whereas cisapride (3 and 10 mg/kg, oral) had no effect under the same conditions. The pharmacological characteristics of DQ-2511 as a gastroprokinetic agent are discussed on the basis of these results.

Topics: Animals; Anti-Ulcer Agents; Benzamides; Gastric Emptying; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasopressins

1. Male, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to permit assessment of the regional haemodynamic responses to human and rat adrenomedullin, to compare the responses to human adrenomedullin to those of human alpha-CGRP in the absence and presence of the CGRP1-receptor antagonist, human alpha-CGRP [8-37], and to determine the involvement of nitric oxide (NO)-mediated mechanisms in the responses to human adrenomedullin, relative to human alpha-CGRP. 2. Human and rat adrenomedullin (0.3, 1, and 3 nmol kg-1, i.v.) caused dose-dependent hypotension and tachycardia, accompanied by increases in renal, mesenteric and hindquarters flows and vascular conductances. At the lowest dose only, the hypotensive and mesenteric vasodilator effects of rat adrenomedullin were significantly greater than those of human adrenomedullin. 3. Human alpha-CGRP at a dose of 1 nmol kg-1 caused hypotension, tachycardia and increases in hindquarters flow and vascular conductance, but reduction in renal and mesenteric flows, and only transient vasodilatations in these vascular beds. These effects were substantially inhibited by human alpha-CGRP [8-37] (100 nmol kg-1 min-1), but those of human adrenomedullin (1 nmol kg-1) were not; indeed, the mesenteric haemodynamic effects of the latter peptide were enhanced by the CGRP1-receptor antagonist. 4. In the presence of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 183 nmol kg-1 min-1), there was only a slight, but significant, inhibition of the hindquarters hyperaemic vasodilator effect of human adrenomedullin, but not that of human alpha-CGRP. 5. These results indicate that the marked regional vasodilator effects of human (and rat) adrenomedullin are largely independent of NO and, in vivo, do not involve CGRP1-receptors.

Topics: Adrenomedullin; Angiotensin II; Animals; Antihypertensive Agents; Arginine; Blood Pressure; Calcitonin Gene-Related Peptide; Catheterization, Peripheral; Dose-Response Relationship, Drug; Heart Rate; Hemodynamics; Humans; Hypertension; Hypotension; Laser-Doppler Flowmetry; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Peptide Fragments; Peptides; Random Allocation; Rats; Regional Blood Flow; Renal Circulation; Tachycardia; Vasopressins

In the absence of the potentially confounding influence of vasopressin in hypertension, the effects of atrial natriuretic peptide (ANP) on arterial blood pressure and renal handling of water and sodium were assessed from comparison of responses to intravenous ANP infusion in anaesthetized vasopressin-deficient New Zealand genetically hypertensive (DI/H) rats and their normotensive substrain (DI/N). After 320 min of hypotonic saline infusion, plasma ANP concentration was significantly higher in DI/H compared with DI/N rats. ANP administration increased circulating ANP concentration in both groups. Plasma angiotensin II concentration was higher in DI/H than in DI/N rats; infusion of ANP raised circulating angiotensin II in both groups though this achieved statistical significance only in DI/N rats. Plasma aldosterone concentrations were initially similar in normotensive and hypertensive animals and, in both, were reduced markedly by I.V. ANP infusion. Administration of ANP produced sustained hypotension in both groups. However, the hypotensive effect of ANP was more pronounced in DI/H compared with DI/N rats. Heart rate was initially similar in the two groups, and infusion of ANP produced no detectable change. By comparison with animals maintained on hormone-free infusate, urine flow increased markedly over the 80 min period of ANP infusion in both groups, by 142% in DI/H rats and 127% in DI/N rats. ANP administration produced a natriuresis in both groups but the increase in Na+ excretion was much greater in DI/H (342%) than in DI/N (139%) rats. It appears from the current study that vasopressin-deficient hypertensive rats are more sensitive to ANP with regard to effects on blood pressure and renal excretion than their vasopressin-deficient normotensive substrain. These differences may, in part, reflect adjustments to long-term elevation in blood pressure and in plasma ANP concentration in hypertension and, in part, rely on the associated disturbances in related endocrine systems.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Endocrine Glands; Heart Rate; Hypertension; Kidney; Male; Rats; Rats, Inbred Strains; Sodium; Vasopressins; Water

1. Tsukuba hypertensive mice (THM) carry both human renin and angiotensinogen genes, and develop hypertension. The animal has high levels of renin activity and angiotensin II concentration in the plasma. 2. Urinary excretion in THM was greater than in the control animal, non-transgenic C57BL/6j. THM showed a greater amount of daily water intake. The osmolality of 24 h urine was lower than that of the control animal. 3. When water was deprived for 12 h and then loaded with 0.25 mL/10 g bodyweight, the osmolality of urine at the first 0-3 h period was the same in THM and control, but significantly lower in THM at the following 3-6 h period, indicating that the urine concentrating activity is insufficient in THM compared with the control animal. 4. Urinary excretion of vasopressin was significantly higher in THM. Plasma aldosterone concentration and urinary excretion of aldosterone were also higher in THM. Plasma potassium level was significantly low. 5. The mechanism underlying the pathophysiology of polyuria is not totally explained; however, hypokalaemia, which was probably the result of hyperaldosteronism, may be at least partially involved, since hypokalaemia is considered to be a factor hampering the action of vasopressin for concentration of urine at the site of the collecting duct of the kidney.

Topics: Aldosterone; Angiotensinogen; Animals; Electrolytes; Humans; Hyperaldosteronism; Hypertension; Kidney Concentrating Ability; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Polyuria; Rats; Renin; Vasopressins

Vascular reactivity, heart rate responses to vasoconstrictor and/or vasodilatator agents and catecholamine and arginine vasopressin turnover were studied in normotensive Wistar Kyoto (WKY), spontaneously hypertensive (SHR), normolipemic Brown Norway (BN) and spontaneously hyperlipemic Yoshida (YOS) anaesthetized rats at 2, 6 and 18 months of age. In this study, we investigated whether ageing and development could affect cardiovascular reactivity to vasoactive substances and catecholamine and arginine vasopressin turnover. No significant changes in the pressor responses to noradrenaline and to carotid sinus baroreceptor stimulation were observed nor were there significant alterations in reflex tachycardia and bradycardia. Arginine vasopressin plasma levels also did not change with ageing and development. On the other hand, the hypotensive responses to isoprenaline decreased in old rats, acetylcholine relaxation effect increased with ageing and development in some rat strains (BN and YOS) and catecholamine plasma levels increased with ageing and development. Our results indicate that during ageing and development, vascular responsiveness to vasoconstrictor and/or vasodilatator agents, as well as amine turnover, may increase, decrease or not change at all depending on the neurotransmission system studied, and on the experimental model and/or animal tested.

Topics: Acetylcholine; Aging; Animals; Arginine; Arterial Occlusive Diseases; Blood Pressure; Carotid Artery Diseases; Catecholamines; Hyperlipidemias; Hypertension; Isoproterenol; Norepinephrine; Rats; Rats, Inbred Strains; Vasomotor System; Vasopressins

Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on conscious spontaneously hypertensive rats (SHR) were investigated. SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W-4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2 were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2 antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats, and V1 antagonist, alone or combined with V2 antagonist, slightly reduced increases in blood pressure of S-2 and S-4 rats without significance. However, V2 antagonist induced significantly massive and hyposmolar urine in W-3 rats compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin contributes to increases in blood pressure via either V1 or V2 receptors less than expected from previous studies with antibodies or peptide antagonists.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Blood Pressure; Hypertension; Male; Osmolar Concentration; Piperidines; Quinolones; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Vasopressin; Urine; Vasopressins

To assess resting haemodynamic status and vasodilator responses in normotensive vasopressin-deficient (DI/N) and hypertensive vasopressin-deficient (DI/H) rats.. DI/N and DI/H rats were chronically instrumented with pulsed Doppler probes and intravascular catheters and were given 3-min infusions of acetylcholine (56 nmol/kg per min), bradykinin (36 nmol/kg per min) or salbutamol (2.1 nmol/kg per min) in the absence and presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 183 nmol/kg per min) or vasopressin (5 pmol/kg per min), to control for the pressor effects of L-NAME.. The DI/H rats had a higher mean arterial blood pressure, lower hindquarters flow and lower vascular conductance than the DI/N rats. In the two strains of rat the haemodynamic responses to L-NAME, as well as to acetylcholine, bradykinin and salbutamol, in the absence or presence of L-NAME, were similar. In both strains of rat the acetylcholine-induced renal vasodilation was blocked by L-NAME, but bradykinin-induced mesenteric and salbutamol-induced hindquarters vasodilation involved L-NAME-sensitive and L-NAME-insensitive components.. There is vasoconstriction in the hindquarters but not in renal and mesenteric vascular beds of DI/H rats. Vasodilator function is not necessarily impaired in congenital hypertension.

Topics: Acetylcholine; Albuterol; Animals; Blood Pressure; Bradykinin; Disease Models, Animal; Hemodynamics; Hypertension; Male; Radioimmunoassay; Rats; Vasodilation; Vasopressins

We investigated effects of beta-adrenoceptor agonists (beta 1-selective: T-1583 and dobutamine, beta 2-selective: fenoterol, non-selective: isoproterenol) on urine outflow rate, blood pressure, heart rate, respiratory rate and rectal temperature. The drugs were applied into the paraventricular nuclei (PVN) of spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Wistar rats. Fenoterol and isoproterenol markedly decreased the urine outflow rate, compared with T-1583 and dobutamine in the rats. There was no marked difference among the three strains in responsiveness to fenoterol and isoproterenol. The antidiuretic effects of fenoterol were inhibited by a beta 2-selective antagonist, butoxamine, more markedly than a beta 1-selective antagonist, atenolol, in SHR; and the inhibitory effects of these drugs were partial in WKY. In Wistar rats, the effect of fenoterol was inhibited by a non-selective beta-antagonist, timolol, but not by atenolol or butoxamine. A vasopressin antagonist (i.v.) did not diminish the antidiuretic effect of fenoterol. Fenoterol reduced the blood pressure in SHR and WKY, but not in Wistar rats. It was suggested that there were predominantly beta 2-adrenoceptors mediating antidiuresis in SHR. In WKY and Wistar rats, however, the beta-adrenoceptor subtypes mediating antidiuresis have yet to be determined. The ability of beta-adrenoceptor agonists to decrease urine outflow rates in SHR was not altered as compared to that in the control rats. beta-Adrenoceptor-mediated antidiuresis was not due to vasopressin release.

Topics: Adrenergic beta-Agonists; Animals; Cardiovascular Physiological Phenomena; Cardiovascular System; Fenoterol; Hypertension; Male; Neurons; Osmotic Pressure; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Receptors, Adrenergic, beta-1; Receptors, Adrenergic, beta-2; Urodynamics; Vasopressins

The rostral ventrolateral medulla (RVLM) is involved in the mediation of cardiovascular responses to peripheral chemoreceptor stimulation. To investigate whether excitatory amino acid inputs in the RVLM are related to the responses to chemoreceptor stimulation, we microinjected kynurenate, an amino acid antagonist, unilaterally into the RVLM and examined its effects on the pressor response to stimulation of carotid body chemoreceptors. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The carotid chemoreceptors were stimulated with isotonic solutions of inorganic phosphate solution. Stimulation of carotid body chemoreceptors produced increases in blood pressure. Kynurenate injected ipsilaterally but not contralaterally into the RVLM markedly inhibited the pressor response to chemoreceptor stimulation. In rats with spinal transection, stimulation of carotid body chemoreceptors also produced increases in blood pressure. The pressor response in rats with spinal transection was inhibited by intravenous injection of a vasopressin antagonist or by kynurenate injected ipsilaterally into the RVLM. Kynurenate injected into the RVLM inhibited the pressor response to NMDA, AMPA and kainate but not to acetylcholine in intact rats. These findings indicate that excitatory amino acid receptors are involved in mediating the pressor response to carotid body chemoreceptor stimulation in the rat RVLM. It appears that the chemoreceptor stimulation produces an increase in vasopressin release and the enhancement of vasopressin release is also mediated by an increase in excitatory amino acid inputs in the RVLM.

Topics: Animals; Blood Pressure; Carotid Body; Cordotomy; Excitatory Amino Acid Antagonists; Heart Rate; Hexamethonium; Hypertension; Kynurenic Acid; Male; Medulla Oblongata; Microinjections; Rats; Rats, Wistar; Receptors, Glutamate; Stimulation, Chemical; Sympathetic Nervous System; Vasopressins

The purpose of this study was to examine comprehensively and quantitatively the effects of sustained hypertension and hypotension on neuronal expression of Fos, the protein product of the proto-oncogene c-fos, in the brain of conscious rabbits. Hypertension or hypotension was produced by continuous intravenous infusion of phenylephrine or nitroprusside, at a rate sufficient to increase or decrease, respectively, arterial pressure by 20-30 mmHg, maintained for a period of 60 min. In comparison with a sham control group of rabbits that were infused with the vehicle solution alone, hypertension induced a significant increase in Fos immunoreactivity in the area postrema, the nucleus tractus solitarii, the caudal and intermediate ventrolateral medulla, the lateral parabrachial nucleus and the central nucleus of the amygdala. Double-labelling for tyrosine hydroxylase and Fos immunoreactivity showed that few (approximately 5%) of the Fos-positive neurons in the caudal and intermediate ventrolateral medulla in this group of animals were also positive for tyrosine hydroxylase. Hypotension also produced a significant increase in Fos immunoreactivity in the above regions, as well as in the rostral ventrolateral medulla, the A5 area, the locus coeruleus and subcoeruleus, the paraventricular nucleus, the supraoptic nucleus, the arcuate nucleus and the medial preoptic area. Approximately 65% of neurons in the rostral, intermediate and caudal ventrolateral medulla that expressed Fos following hypotension were also positive for tyrosine hydroxylase. Similarly, in the pons, approximately 75% of Fos-positive cells in the locus coeruleus, subcoeruleus and A5 area were positive for tyrosine hydroxylase. In the hypothalamus, 92% of Fos-positive neurons in the supraoptic nucleus, and 37% of Fos-positive neurons in the paraventricular nucleus, were immunoreactive for vasopressin. Our results demonstrate that hypertension and hypotension induce reproducible and specific patterns of Fos expression in the brainstem and forebrain. The distribution patterns and chemical characteristics of Fos-positive neurons following sustained hypertension or hypotension are significantly different. In particular, hypotension, but not hypertension, caused Fos expression in many tyrosine hydroxylase-positive cells within all pontomedullary catecholamine cell groups.

Topics: Animals; Brain; Brain Chemistry; Cell Nucleus; Female; Hypertension; Hypotension; Immunohistochemistry; Male; Neurons; Perfusion; Proto-Oncogene Proteins c-fos; Rabbits; Tyrosine 3-Monooxygenase; Vasopressins

Vasopressin (VP) levels were evaluated by radioimmunoassay (RIA) in the arterial (A), peripheral (Vp) and jugular (Vj) vein blood and in CSF in 102 patients with brain tumors. In 60 cases the patients' state was complicated by brain edema (BE) and hemodynamic disturbances (HDD). The obtained data revealed significantly higher VP levels: 1) in A, Vp and CSF in patients with BE (Group A) in comparison with patients without BE (Group B), 2) in Vj in patients with HDD only (Group Bc) and 3) in Vp in patients with HDD and BE (Group Ac) in comparison with Group Bc (p < 0.05). There were marked extremely high VP levels in Vj in patients with severe haemorrhage, tachycardia and high blood pressure (BP) and in CSF in patients with tachycardia, high BP and cardiac arrest (p < 0.05 correspondingly in each of the cases). Our results on a clinical basis confirmed CSF VP influence on BE development. We also confirmed the neurohumoral (through blood) and neurotransmitter (possibly through CSF and/or vasopressinergic pathways) VP influences on cardiovascular regulation mechanisms. We content that this is a pathogenetic basis for application of VP direct or indirect antagonists for preventing and treating brain edema in neurosurgical patients.

Topics: Adolescent; Adult; Aged; Blood-Brain Barrier; Brain Edema; Brain Neoplasms; Cerebral Hemorrhage; Child; Child, Preschool; Female; Heart Arrest; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Postoperative Complications; Radioimmunoassay; Synaptic Transmission; Tachycardia; Vasopressins

The study of renin-angiotensin-aldosterone (RAA) and vasopressin (VP) systems in neurosurgical patients with brain tumors and brain edema (BE) had revealed an excessive activity of these systems with secondary hyperaldosteronism especially with BE that proves the pathogenetic role of these systems. Measurement of Aldosterone (Ald) in CSF may serve as a diagnostic test to help manage the patient's clinical condition. Mechanisms of Ald penetration in CSF assumed to be the result of blood-brain-barrier (BBB) destruction (especially in astrocytomas) and/or the mediation by neuropeptides (for example increasing activity of VP V1-receptors). Results serve as a basis for application of the neuropeptide and hormone antagonists and inhibitors on all stages of cascade reactions taking part in the water and sodium retention.

Topics: Adolescent; Adult; Aged; Aldosterone; Astrocytoma; Blood-Brain Barrier; Brain Edema; Brain Neoplasms; Cerebral Hemorrhage; Child; Child, Preschool; Female; Heart Arrest; Hemodynamics; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Postoperative Complications; Prognosis; Radioimmunoassay; Renin-Angiotensin System; Tachycardia; Vasopressins

In an earlier study, we reported that chronic intravenous administration of the V1 agonist [Phe2,Ile3,Orn8]vasopressin (V1AG) results in sustained hypertension. The present study was designed to determine whether V1-induced hypertension may be related specifically to intrarenal actions of this peptide. Chronic infusion of the V1 agonist into the medullary interstitial space of a single remaining kidney of normal, conscious Sprague-Dawley rats at the rate of 2 ng.kg-1.min-1 for 14 days resulted in a sustained rise of 18 mmHg of mean arterial pressure (MAP). After withdrawal of V1AG, MAP returned to the baseline level. During the first day of V1AG infusion, there was a net loss of body sodium and no evidence of fluid retention throughout the period of hypertension. Plasma osmolality, sodium and potassium concentration, and water intake and body weight were not significantly affected by medullary interstitial infusion of V1AG. Renal medullary interstitial infusion of an equimolar amount of arginine vasopressin (AVP) did not affect MAP. Chronic medullary interstitial infusion of the selective V1 antagonist d(CH2)5[Tyr(Me)2,Ala-NH(2)9]AVP in equimolar amounts (2.5 ng.kg-1.min-1) prevented the MAP increase elicited by intravenous V1AG. However, intravenous administration of the V1 antagonist at the same rate together with V1AG (n = 7) failed to prevent hypertension. The results indicate that hypertension can be elicited by chronic stimulation of renal medullary V1 vasopressin receptors. They also suggest that some V2 agonistic properties of AVP may restrict the hypertensive action of this hormone. The mechanism for the rise of arterial pressure remains to be determined.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Diuresis; Drug Administration Schedule; Heart Rate; Hypertension; Infusions, Parenteral; Kidney Medulla; Male; Ornipressin; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Time Factors; Vasopressins

The mechanisms whereby the continuous administration of initially subpressor doses of angiotensin II (ANG II) leads to pressor hyperresponsiveness and gradual development of hypertension were investigated. Male Sprague-Dawley rats (350 to 400 g) were given ANG II intraperitoneally, 200 ng/kg/min, for 24 h, 7 to 10 days, or 6 weeks. Vehicle-infused rats were controls. Pressor responses to incremental doses of ANG II, norepinephrine (NE), and serotonin were measured in chloralose-anesthetized rats, before and after neurohumoral blockade, and the main findings were confirmed in awake, free-moving rats with implanted catheters. Pressure responses to ANG II and NE were also measured in the isolated, pump-perfused mesenteric circulation of rats after 7 to 10 days of ANG II or sham infusion. Compared with control rats, there were no hemodynamic changes in ANG II-treated rats at 24 h. After 7 to 10 days of ANG II treatment, tail systolic blood pressure rose by 13 mm Hg (P < .01) and pressor responses to ANG II (P < .01) but not to NE or serotonin were increased. Pressor hyperresponsiveness was due in part to potentiation of vascular responses because pressure responses to ANG II (P < .002) but not to NE were also increased in the mesenteric circulation of ANG II-treated rats. By 6 weeks, mild hypertension was well established in ANG II-treated rats and pressor responses were increased to both ANG II (P < .05) and NE (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acid Sequence; Anesthesia; Angiotensin II; Animals; Blood Pressure; Body Weight; Chloralose; Heart Rate; Hypertension; Injections, Intraperitoneal; Male; Molecular Sequence Data; Norepinephrine; Rats; Rats, Sprague-Dawley; Renin; Serotonin; Splanchnic Circulation; Vasopressins

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Diuresis; Heart Rate; Hormones; Hypertension; Injections, Intravenous; Male; Natriuresis; Ornipressin; Rats; Rats, Sprague-Dawley; Time Factors; Vasopressins

The present study was designed to investigate the effect of a lack of vasopressin resulting from electrolytic lesion of the median eminence of the hypothalamus on the acute 45-min aortic coarctation hypertension elicited in conscious rats by means of a pneumatic cuff placed around the aorta above the renal arteries. Forty-eight hours after lesion, aortic constriction elicited a prompt (5-min) rise in mean carotid pressure from 115 +/- 2 to 149 +/- 2 mmHg, followed by a gradual decline to 129 +/- 2 mmHg. In contrast, sham-lesioned rats exhibited a prompt hypertensive response from 118 +/- 2 to 157 +/- 2 mmHg that leveled off throughout the experiment. Lesioned rats treated with saralasin presented a blunted hypertensive response (within 125 +/- 2 to 130 +/- 2 mmHg), whereas sham-lesioned rats showed only a delay in the onset of hypertension. The hypertensive response of lesioned rats was unaffected by the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP, whereas sham-lesioned rats submitted to this treatment presented a prompt rise in pressure followed by a gradual decline at the end of the experiment. Lesioned and sham-lesioned rats treated with saralasin plus vasopressin antagonist showed a blunted hypertensive response throughout the experiment. These data demonstrate that the integrity of the median eminence plays a pivotal role in the maintenance (30-45 min) of acute aortic coarctation hypertension, presumably involving the release of vasopressin from the neurohypophysis, whereas angiotensin II mainly accounts for the prompt (5-15 min) rise in pressure.

Topics: Acute Disease; Animals; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Hypertension; Male; Median Eminence; Rats; Rats, Wistar; Saralasin; Vasopressins

Vasopressin has been shown to act at the area postrema to increase the sensitivity of the baroreceptor reflex. We have previously demonstrated that microinjection of vasopressin into the area postrema of Sprague-Dawley rats elicits pressor effects. We report here that vasopressin microinjection into the area postrema of spontaneously hypertensive rats is without effect on blood pressure, whereas microinjection into age-matched Wistar-Kyoto controls results in significant increases in blood pressure at 50 and 100 pg. These results suggest an altered sensitivity of the area postrema to vasopressin in this genetic model of hypertension.

Topics: Animals; Blood Pressure; Heart Rate; Hemodynamics; Hypertension; Male; Medulla Oblongata; Microinjections; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasopressins

The effects of extracellular Cl- concentration ([Cl-]o) on cultured mesangial cells from spontaneously hypertensive rats (SHR) were examined. Angiotensin II (ANG II)- and vasopressin (VP)-induced cell contraction and Ca2+ transients of SHR mesangial cells were unaffected when the cells were preincubated with 10 mM [Cl-]o, while obvious suppression of the responses to these agents was observed in Wistar-Kyoto (WKY) mesangial cells. Enhanced prostaglandin E2 (PGE2) production was elicited by a decrease in [Cl-]o in WKY mesangial cells. In contrast, PGE2 synthesis by SHR mesangial cells was not enhanced by low [Cl-]o. However, ANG II-stimulated PGE2 production and the attenuation of ANG II-induced cell contraction and Ca2+ transients by the addition of exogenous PGE2 were present equally in both WKY and SHR mesangial cells. Based on these findings, we conclude that the absence of modification of mesangial cell function by [Cl-]o in SHR is due to the inability of low [Cl-]o to enhance PGE2 production. Insensitivity of SHR mesangial cells to changes in [Cl-]o might underlie the dysregulation of renal function in SHR.

Topics: Angiotensin II; Animals; Calcium; Chlorides; Dinoprostone; Glomerular Mesangium; Hypertension; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction; Vasopressins

We explored the role of angiotensin II and vasopressin in the maintenance of blood pressure during the nephrotic syndrome of adriamycin-induced nephropathy in rats. All 91 rats treated with adriamycin developed chronic renal failure with nephrotic syndrome, which was more pronounced in the normotensive rats than the 35% who became hypertensive. Angiotensin II blockade with DuP 753 produced a significantly greater hypotensive response in both the adriamycin-hypertensive (-16 +/- 3 mm Hg) and adriamycin-normotensive (-14 +/- 5 mm Hg) groups than the saline-treated controls (-5 +/- 1 mm Hg, P < .05). Vasopressin blockade with either a V1V2 inhibitor or a selective V1 inhibitor produced a hypotensive response in adriamycin-hypertensive rats only (by -16 +/- 4 and -17 +/- 2 mm Hg, respectively, P < .01), although the nonselective vasopressin inhibitor produced similar fluid loss and body weight reduction in all three groups. The data suggest that in adriamycin-induced nephropathy with nephrotic syndrome, angiotensin II contributes to blood pressure maintenance in both hypertensive and normotensive animals, whereas the pressor action of vasopressin contributes to elevated blood pressure in hypertensive animals only.

Topics: Angiotensin II; Animals; Biphenyl Compounds; Blood Pressure; Cholesterol; Creatinine; Doxorubicin; Hypertension; Imidazoles; Kidney; Kidney Failure, Chronic; Losartan; Male; Nephrotic Syndrome; Potassium; Rats; Rats, Wistar; Serum Albumin; Sodium; Tetrazoles; Time Factors; Urea; Vasopressins

To appreciate the role of some neuropeptides in the antihypertensive mechanism of clonidine, 17 patients with essential hypertension were given po clonidine 150 micrograms tid for 3 d. Plasma atrial natriuretic factor (ANF), vasopressin (Vas), and dynorphin A (Dyn A) were measured by radioimmunoassay. After the treatment, mean blood pressure (MBP), heart rate and 24 h urine norepinephrine, epinephrine were decreased, but no change was found in plasma Dyn A. The magnitudes of increased ANF and decreased Vas were correlated with the decreased MBP (r = -0.57 and 0.53, respectively, P < 0.05). These results suggest that both ANF and Vas are involved in the antihypertensive mechanism of clonidine.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Clonidine; Dynorphins; Female; Humans; Hypertension; Male; Middle Aged; Radioimmunoassay; Vasopressins

To investigate the involvement of the sympathoinhibitory effect of imidapril and enalapril in their antihypertensive effect at a clinically reasonable dose, we studied whether some responses induced by the stimulation of the sympathetic nervous system (SNS) were affected by intravenous administration of imidaprilat and enalaprilat in curarized pithed spontaneously hypertensive rats. Imidaprilat and enalaprilat (both at 100 micrograms/kg, i.v.), which are active metabolites of imidapril and enalapril, respectively, suppressed the pressor responses to electrical stimulation (ES) of the spinal cord (T1-L7) and exogenous noradrenaline (NA). The pressor responses to NA were significantly suppressed after either alpha 1- or alpha 2-adrenoceptors were blocked. Furthermore, imidaprilat (100 micrograms/kg, i.v.) suppressed these reduced responses. When the reduced basal blood pressure was restored by vasopressin infusion, imidaprilat and enalaprilat (both at 100 micrograms/kg, i.v.) did not suppress the responses to ES and exogenous alpha-adrenoceptor agonists. They affected neither basal plasma concentrations of NA and adrenaline nor ES-induced increase of these catecholamines. These results suggest that the suppressive effects of imidaprilat and enalaprilat on the pressor responses to ES and alpha-adrenoceptors agonists are apparently observed in pithed SHR because of a reduction of vascular tone and that imidapril and enalapril do not lower the blood pressure through suppressing SNS.

Topics: Adrenergic alpha-Antagonists; Animals; Antihypertensive Agents; Blood Pressure; Chromatography, High Pressure Liquid; Decerebrate State; Electric Stimulation; Enalapril; Enalaprilat; Epinephrine; Hypertension; Imidazoles; Imidazolidines; Male; Norepinephrine; Rats; Rats, Inbred SHR; Spinal Cord; Sympathetic Nervous System; Vasopressins

Blood contents of pressor peptide hormones vasopressin and angiotonin II were studied in patients with neuro-endocrine syndrome before and after single intake and prolonged treatment with anti-serotonin drug peritol and cholinergic agent parlodel which affect biogenic amine metabolism and, consequently, influence blood pressure. Single doses of the drugs were established to cause different blood dynamics of vasopressin and angiotonin II which classified as marked and paradoxic reactions on peritol and parlodel used separately and associatively. Fall of blood vasopressin content induced by single dose of parlodel was accompanied by blood pressure decrease. Tree-week treatment with peritol and parlodel exerted hypotensive effect and significantly reduced vasopressin blood content.

Topics: Adolescent; Adult; Angiotensin II; Biogenic Amines; Blood Pressure; Bromocriptine; Chronic Disease; Cyproheptadine; Drug Evaluation; Female; Humans; Hypertension; Hypothalamic Diseases; Male; Middle Aged; Syndrome; Time Factors; Vasopressins

Subjects with initially increased level of arterial pressure were shown to have a higher contents of vasopressin in the blood plasma and of cortisol in the saliva. All the subjects revealed an increased systolic and diastolic blood pressure in response to a psycho-emotional load. The levels of cortisol and vasopressin did not increase at that. Neither the adrenaline level changed whereas the noradrenaline level increased. The latter increased more in the subjects with a milder form of arterial hypertension. The data obtained suggest that the reactivity of the sympatho-adrenal system is higher in the subjects with an increased arterial pressure.

Topics: Adrenal Glands; Blood Pressure; Catecholamines; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Pulse; Saliva; Stress, Psychological; Sympathetic Nervous System; Vasopressins

To determine the roles of vasopressin, the renin-angiotensin system and sex in the pathogenesis of salt-sensitive hypertension in the Dahl rat.. The effects of 12 days' treatment with a non-peptide, orally effective V1 antagonist (OPC-21,268) and captopril, individually or together, were compared in male and female Dahl salt-sensitive rats after 10 days on a high-salt diet.. OPC-21,268 was given in the food, and captopril was administered with osmotic pumps implanted subcutaneously.. Systolic blood pressure (SBP) reached a higher level in untreated males than in untreated females. V1 blockade in males prevented any further increase in SBP during the first week of treatment, but SBP rose thereafter towards the levels found in the untreated males. In females OPC-21,268 had no effect. In males captopril prevented any further increase in SBP. There was no effect of captopril in females during the first week of treatment, but SBP fell to pretreatment levels during the second week. Combined treatment with OPC-21,268 and captopril in males had a smaller antihypertensive effect than either drug alone. In females combined treatment prevented any further increase in SBP.. These findings suggest that both vasopressin and the renin-angiotensin system contribute to the pathogenesis of Dahl salt-sensitive hypertension, but that other factors, possibly including the sympathetic nervous system, are also involved. Sex also affects the severity of this form of hypertension and influences the relative roles of vasopressin and the renin-angiotensin system. It is likely that the gonadal steroid hormones modulate the activity of the pathogenetic factors in this form of hypertension at a central or peripheral level.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Captopril; Circadian Rhythm; Diet; Female; Hypertension; Male; Piperidines; Quinolones; Rats; Rats, Mutant Strains; Renin-Angiotensin System; Sex Characteristics; Sodium Chloride; Vasopressins

Arterial pressure, sodium excretion, urine output, and plasma atrial natriuretic peptide (ANP) concentrations were measured before, during, and after a 3-h i.v. infusion of arginine-vasopressin (vasopressin; 20 ng/kg/min) in conscious Doca-salt hypertensive rats. Arterial pressure was 166 +/- 8 mm Hg before the infusion of vasopressin; in comparison, pressure was only 130 +/- 4 mm Hg 5 h after stopping the infusion. The fall in pressure after withdrawal of an equipressor dose of phenylephrine in hypertensive animals was much less. In sham normotensive rats, pressure did not fall below control levels after stopping either the vasopressin or phenylephrine infusion. Sodium excretion rates were higher during infusions of vasopressin than during phenylephrine infusions. However, the elevations observed during vasopressin were similar in the hypertensive (25.3 +/- 4.9 mumol/kg/min) and normotensive (22.9 +/- 2.7 mumol/kg/min) groups. Urinary output increased to a greater extent in the hypertensive rats during the infusions of both vasopressin and phenylephrine, but the increases were similar for the 2 pressor agents. Plasma levels of ANP were elevated during the infusions of vasopressin in the normotensive rats, but not in hypertensive rats. The results indicate that the fall in pressure associated with cessation of a pressor dose of vasopressin appears specific to the hypertensive state, and relatively specific to vasopressin. This withdrawal-induced antihypertensive phenomenon (WAP) does not appear to be due solely to the preceding natriuresis and diuresis during the infusion of vasopressin. However, because the hypertensive animal may be more sensitive to a given degree of sodium loss, the possibility that the natriuresis could play a contributing or permissive role cannot be excluded.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Desoxycorticosterone; Hematocrit; Hypertension; Natriuresis; Osmolar Concentration; Rats; Rats, Sprague-Dawley; Sodium; Vasopressins

Continuous infusion of IV vasopressin have been widely used to lower portal pressure and reduce bleeding from esophageal varices. Recently, the combination of vasopressin and nitroglycerin has been noted to be superior to vasopressin alone. This is due to the ability of nitroglycerin to reduce the detrimental effects of vasopressin while preserving its beneficial effects. In September 1989 the authors initiated a protocol in the medical intensive care unit of a large university teaching center that directed caregivers in the simultaneous use of vasopressin and nitroglycerin for use in variceal bleeding.. To determine whether the protocol was being used correctly and whether the addition of nitroglycerin produced the desired cardiovascular effects.. Nineteen patients (25 separate episodes) assigned to the vasopressin/nitroglycerin protocol were monitored retrospectively over a 20-month period for a total of 1068 hours of vasopressin/nitroglycerin infusion. Twenty-four patients received nitroglycerin at 10 to 50 micrograms per minute, 13 at 50 to 100 micrograms per minute and 6 at 100 to 400 micrograms per minute.. Nitroglycerin dosage was not advanced appropriately in 78% of episodes despite evidence of bradycardia, hypertension and peripheral vasoconstriction.. Revision of the protocol, giving additional guidance to clinicians on assessment and nitroglycerin advancement, was necessary and was accomplished.

Topics: Bradycardia; Clinical Protocols; Constriction, Pathologic; Drug Monitoring; Drug Therapy, Combination; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Heart Rate; Hemodynamics; Humans; Hypertension; Infusions, Intravenous; Nitroglycerin; Nursing Assessment; Nursing Evaluation Research; Nursing Records; Patient Care Planning; Practice Patterns, Physicians'; Retrospective Studies; Vasopressins

Topics: Adult; Aged; Aging; Arginine Vasopressin; Black People; Blood Pressure; Humans; Hypertension; Middle Aged; Posture; Racial Groups; Vasopressins; White People

Recent studies have found vasopressin to be antinatriuretic as well as antidiuretic. We therefore wished to determine the endogenous renal activity of vasopressin in spontaneously hypertensive rats (SHR) and one-kidney, one clip hypertensive (1K1C) rats.. The renal effects of a vasopressin (V2) antagonist, [d(CH2)5,D-Ile2,Ile4]-arginine vasopressin (0, 10 or 30 nmol/kg), were compared in SHR and 1K1C rats and their respective controls, the Wistar-Kyoto (WKY) rat and the Sprague-Dawley rat.. The V2 antagonist produced a dose-related increase in urine flow rate and free water clearance in all groups studied (WKY rats, SHR, Sprague-Dawley rats and 1K1C rats). Sodium excretion and osmolar clearance were increased only in the WKY rats and 1K1C rats. The response in the SHR was significantly less than that observed in the WKY rats. At both doses of V2 antagonist investigated, the urine flow rate was two- to threefold greater in the WKY rats than in SHR, in spite of similar control levels. Conversely, the response observed in the acquired model of hypertension (1K1C rats) at the one dose of V2 antagonist investigated (30 nmol/kg) was similar to that found in the control Sprague-Dawley rats, suggesting that the decreased response observed in SHR was not secondary to the increased blood pressure.. These data demonstrate that the endogenous level of renal activity of vasopressin in SHR is suppressed compared with control WKY rats.

Topics: Animals; Arginine Vasopressin; Diuresis; Dose-Response Relationship, Drug; Hypertension; Kidney; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Receptors, Vasopressin; Sodium; Vasopressins

1. The present study was undertaken to test whether insulin acts as a pressor agent and causes hypertension in rats. 2. Insulin at doses of 10 or 100 units day-1 kg-1 was administered daily by subcutaneous injection to normal rats for 6 weeks. As it has been suggested that sodium retention plays a major role in the putative hypertensive activity of this hormone, insulin was also administered to saline- (1% NaCl) drinking rats according to the same protocol. Water- and saline-drinking rats served as controls. 3. After 6 weeks of insulin treatment, the mean arterial blood pressure did not increase in any of the insulin-treated or the insulin-salt-treated groups. However, in both insulin-salt-treated groups, absolute and relative ventricular and renal hypertrophy with increased ventricular water content as well as increased urine output with reduced osmolality were observed. 4. All insulin-treated groups showed increased plasma levels of glucose, insulin and antidiuretic hormone when compared with their respective controls. 5. These results demonstrate that chronic insulin treatment did not increase blood pressure in rats, even when drinking water was supplemented with NaCl, and suggest that a polyuria-polydipsia syndrome was present in both insulin-salt-treated groups. Moreover, increased plasma levels of antidiuretic hormone were observed in all insulin-treated groups.

Topics: Animals; Blood Glucose; Body Weight; Electrolytes; Hypertension; Insulin; Kidney; Male; Organ Size; Rats; Rats, Wistar; Sodium Chloride; Vasopressins

The goal of this study was to determine whether enhanced vascular responsiveness during the development of perinephritic hypertension is selective or nonspecific. The effects of graded infusions of norepinephrine (NE), phenylephrine (PE), angiotensin II (ANG II), and vasopressin (VP) were examined on mean arterial pressure, total peripheral resistance (TPR), and aortic pressure-diameter relationships in conscious dogs. NE increased TPR significantly greater (P < 0.01) in hypertension than normotension, as did PE infusion, whereas ANG II and VP increased TPR similarly before and after hypertension. Analysis of aortic pressure-diameter relationships also demonstrated significant (P < 0.05) shifts in response to NE and PE, but not ANG II and VP, during the development of hypertension. In normotensive dogs, low doses of ANG II infusion also enhanced the vasoconstrictor response not only to NE and PE but also to VP. In contrast to what was observed in hypertension, in the presence of ANG II infusion after ganglionic blockade, enhanced responses to PE and NE were no longer observed. The alpha 1-adrenergic receptor density in membrane preparations from aortic tissue, as determined by [3H]prazosin binding, was higher (P < 0.05) in hypertensive dogs than control dogs. Thus the vascular responsiveness in the aorta and resistance vessels is enhanced to alpha 1-adrenergic stimulation, but not to all vasoconstrictors, during developing perinephritic hypertension. The mechanism appears to involve increased alpha 1-adrenergic receptor density.

Topics: Angiotensin II; Animals; Aorta; Blood Pressure; Cell Membrane; Consciousness; Dogs; Female; Hypertension; Male; Phenylephrine; Prazosin; Receptors, Adrenergic, alpha; Vascular Resistance; Vasoconstriction; Vasopressins

Endothelium-dependent relaxation of mesenteric resistance arteries of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats was studied. Acetylcholine-induced relaxation of SHR vessels precontracted with 10 microM norepinephrine was endothelium dependent and attenuated compared with WKY vessels. The impaired response of SHR vessels was normalized by inhibition of cyclooxygenase with indomethacin. Blockade of nitric oxide synthetase with NG-nitro L-arginine methyl ester (L-NAME) or inhibition of guanylate cyclase with methylene blue attenuated acetylcholine-induced relaxation of norepinephrine-contracted SHR vessels but had no effect on WKY vessels. When vessels were precontracted with 30 nM arginine vasopressin, acetylcholine induced similar degrees of relaxation in both strains. A similar response was detected when lysine vasopressin was used to induce tone. Indomethacin had no effect on relaxation responses of SHR and WKY vessels precontracted with either form of vasopressin. L-NAME and methylene blue partially inhibited acetylcholine-induced relaxation of vasopressin-contracted vessels from both strains. Acetylcholine added at baseline did not induce contraction of vessels from either strain. It is concluded that endothelium-dependent relaxation of SHR resistance arteries is not impaired under all circumstances. Acetylcholine-induced relaxation may be suppressed in SHR resistance arteries when norepinephrine is used to induce contraction as a result of catecholamine-induced production of an endothelium-derived contracting factor. Vasopressin, on the other hand, does not elicit production of this contracting factor and may enhance the vasorelaxant action of acetylcholine in resistance arteries of both strains via actions on endothelial or vascular smooth muscle cells.

Topics: Acetylcholine; Animals; Endothelium, Vascular; Hypertension; In Vitro Techniques; Male; Mesenteric Arteries; Muscle Relaxation; Muscle, Smooth, Vascular; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vascular Resistance; Vasopressins

A group of 41-year-old hypertensive men (n = 35, blood pressure (BP) 149.9 +/- 2.1/98.9 +/- 1.1 mmHg, mean +/- SEM) who had never received treatment for their condition were compared with hypertensive women of the same age (n = 18, BP 155.9 +/- 4.3/98.1 +/- 1.6 mmHg) with comparable body mass index (BMI, 25.9 +/- 0.5 vs. 24.9 +/- 4.5 kg m-2) who, also, had never received treatment. The lipid profile was more atherogenic in the men, with lower HDL cholesterol (1.21 +/- 0.04 vs. 1.38 +/- 0.06 mmol l-1, P = 0.04), higher total cholesterol (6.04 +/- 0.14 vs. 5.54 +/- 0.18 mmol l-1, P = 0.04) and triglycerides (1.80 +/- 0.16 vs. 0.96 +/- 0.10 mmol l-1, P < 0.001). The hypertensive men had higher haemoglobin (P < 0.001) and haematocrit. Plasma catecholamines were inversely related to BMI in the women only (r = -0.52, P < 0.05 for both noradrenaline and adrenaline). Women with BMI above 25 kg m-2 had significantly lower arterial plasma adrenaline and noradrenaline than those with BMI below 25 kg m-2 (28 +/- 5 vs. 78 +/- 16 pg ml-1, P < 0.01 and 101 +/- 17 vs. 206 +/- 33 pg ml-1, P < 0.01 respectively). A negative curvilinear relationship appeared between arterial adrenaline and insulin (r = 0.49, P = 0.05). These results suggest a male propensity for athero-thrombogenic risk factors in otherwise comparable hypertensive subjects. A close relationship between metabolic risk factors within the normal range seems to exist even in hypertensive women. The decreased sympathetic activity at rest in the obese hypertensive women indicates different pathophysiological mechanism for hypertension in lean and obese. Decreased sympathetic activity and thus reduced energy expenditure, promotes a risk for weight gain, and could explain the inverse relationship between insulin and adrenaline.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Catecholamines; Electrolytes; Female; Hematocrit; Hemoglobins; Humans; Hypertension; Insulin; Lipids; Male; Renin; Risk Factors; Sex Characteristics; Vasopressins

Single-mass primary cultures were used for as long as 5 wk as the source of subcultured vascular smooth muscle cells for the study of their change of shape on the addition of agonists. We have compared the responses to angiotensin II, vasopressin, norepinephrine, and serotonin of myocytes derived from three different areas or the thoracic aorta (aortic arch and midthoracic and diaphragm areas) of adult Wistar-Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHR). Once in secondary culture, vascular myocytes displayed different mean sizes according to their origin along the organ, as previously described in freshly dispersed aortic myocyte suspensions. Responses of the cells from the area of the aortic arch of both strains had the maximal amplitude to all agonists. Angiotensin and norepinephrine were more potent on myocytes derived from the three areas in SHR than in WKY. As this hypersensitivity persisted even after 5 wk in culture, it is believed to be pressure independent and thus might have a genetic rather than an adaptive origin.

Topics: Angiotensin II; Animals; Aorta; Aorta, Thoracic; Diaphragm; Hypertension; Male; Muscle, Smooth, Vascular; Myocardial Contraction; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Serotonin; Vasopressins

Transient diabetes insipidus of pregnancy (TDIP) is associated with elevated activity of vasopressinase, a plasma enzyme that opens the vasopressin (AVP) ring to produce a linear peptide that we have named vasopressinase-altered vasopressin (VAV). VAV may play a role in the pathogenesis of the arterial hypertension associated with TDIP. We sought to determine if VAV elevates arterial pressure, the potency of VAV relative to that of AVP, and whether the peptide binds to the vascular AVP receptor. AVP was incubated with vasopressinase and VAV was separated from residual AVP by high-pressure liquid chromatography. Intravenous bolus administration of VAV or AVP to ganglionic blocked rats produced dose-dependent increases in arterial pressure, with VAV demonstrating approximately 6000-fold lower potency than AVP. Vasopressin receptor blockade abolished the response to both AVP and VAV. These results suggests that high levels of VAV may contribute to the hypertension seen in TDIP.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Dose-Response Relationship, Drug; Hypertension; Male; Rats; Rats, Sprague-Dawley; Vasopressins

Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominantly express AT1 ANG II receptors. In contrast, AT2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT1 and AT2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 microliters) were determined 10 minutes after i.c.v. injection of either the AT1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 10.0 micrograms), the AT2 receptor ligand PD 123319 (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both. In control rats, i.c.v. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II-induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG-II-induced pressor effects may involve activation of multiple receptor subtypes.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Brain; Disease Models, Animal; Heart Rate; Hypertension; Imidazoles; Injections, Intraventricular; Losartan; Male; Pyridines; Rats; Rats, Inbred SHR; Receptors, Angiotensin; Sympathetic Nervous System; Tetrazoles; Vasopressins

The hemodynamic and metabolic effects of 11 days of sham (saline) and corticotropin injection were examined in five different strains of rats: Sprague-Dawley, spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), Brattleboro, and Long Evans. Corticotropin significantly increased systolic blood pressure (SBP) compared with sham injection in all strains: final SBP in Sprague-Dawley was 108 +/- 5 mm Hg corticotropin, 94 +/- 4 mm Hg sham; SHR 146 +/- 6 mm Hg corticotropin, 141 +/- 3 mm Hg sham; WKY 117 +/- 3 mm Hg corticotropin, 103 +/- 3 mm Hg sham; Brattleboro 108 +/- 5 mm Hg corticotropin, 93 +/- 2 mm Hg sham; and Long Evans 103 +/- 5 mm Hg corticotropin, 90 +/- 4 mm Hg sham (P less than .001). Corticotropin also produced a decrease in body weight and increases in water intake and urine output. Increases in urine electrolyte excretion were seen in some, but not all strains. The rise in pressure in the Brattleboro rats indicated that vasopressin is not essential for the corticotropin-induced rise in pressure. Blood pressure rises in SHR were not exaggerated. Withdrawal of corticotropin in Sprague-Dawley rats led to rapid reversal of the corticotropin-induced hemodynamic and metabolic changes. Thus, strain does not appear to be an important factor in corticotropin hypertension in the rat, in contrast to deoxycorticosterone hypertension.

Topics: Adrenocorticotropic Hormone; Analysis of Variance; Animals; Blood Pressure; Electrolytes; Homeostasis; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Vasopressins

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Cyclic AMP; Cyclic GMP; Diagnosis, Differential; Electrocardiography; Exercise Test; Humans; Hypertension; Hypertension, Renal; Male; Renin-Angiotensin System; Vasopressins

To test the hypothesis that enhanced expression of the vasopressin gene accompanies the development of deoxycorticosterone acetate (DOCA)-salt hypertension in the rat and to compare the response with those observed during chronic hypernatremia.. Transcript levels were determined by measurement of vasopressin messenger RNA (mRNA) in the supraoptic nucleus and paraventricular nucleus by in situ hybridization, autoradiography and image analysis. Plasma, urinary and pituitary vasopressin were determined by radioimmunoassay.. High-resolution localization and measurement of specific mRNA in the supraoptic and paraventricular nuclei before and during development of DOCA-salt hypertension were compared with corresponding results in both age-matched controls and normal rats that drank hypertonic saline.. Vasopressin mRNA levels were increased in the paraventricular nucleus during the established and chronic stages of DOCA-salt hypertension, but were unchanged in the supraoptic nucleus. Urinary excretion of vasopressin was increased in the prehypertensive, established and chronic phases of DOCA-salt hypertension, whereas plasma vasopressin levels were increased only in the chronic phase. Pituitary vasopressin levels were unchanged. In comparative studies, vasopressin mRNA levels in both the supraoptic and paraventricular nuclei and plasma vasopressin were significantly increased in normal rats drinking 2% saline.. Whereas hypernatremic rats showed markedly elevated vasopressin transcripts in the supraoptic and paraventricular nuclei, DOCA-salt hypertension is associated with increased vasopressin mRNA in the paraventricular but not the supraoptic nucleus. The response in the paraventricular nucleus may explain part of the increased peripheral vasopressin levels and suggests that this nucleus makes a critical contribution to the pathogenesis of DOCA-salt hypertension.

Topics: Animals; Desoxycorticosterone; Gene Expression; Hypernatremia; Hypertension; Male; Models, Cardiovascular; Paraventricular Hypothalamic Nucleus; Pituitary Gland; Rats; Rats, Sprague-Dawley; RNA, Messenger; Supraoptic Nucleus; Transcription, Genetic; Vasopressins

Aim of the study was to evaluate the effect of cardiopulmonary receptors activation and deactivation on antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) incretion in hypertensive and normotensive subjects. Twenty-one male subjects, 7 normotensives and 14 mild hypertensives, 7 without and 7 with left ventricular hypertrophy (LVH) were admitted to the study. Each subject underwent selective loading and unloading of cardiopulmonary receptors, by application of a positive (LBPP) or negative (LBNP) pressure to the lower body. Blood samples were taken for measurement of ANP, ADH, PRA, immunoreactive renin, aldosterone, noradrenaline and adrenaline. ADH plasma concentration increased during cardiopulmonary receptors inhibition, but this increase became statistically significant (p less than 0.05) at a step of LBNP (-40 mm Hg), in which an involvement of the sinoaortic receptors cannot be excluded. ANP plasma levels increased progressively during LBPP (p less than 0.05 at least). These changes were significantly reduced in hypertensive patients with LVH.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Cardiomegaly; Hemodynamics; Hormones; Humans; Hypertension; Lower Body Negative Pressure; Male; Middle Aged; Pressoreceptors; Pressure; Vasopressins

1. The mechanism of the antihypertensive effects of n-3 fatty acids were examined in spontaneously hypertensive rats (SHR) by feeding 'Max EPA' fish oil or hydrogenated coconut oil and determining the responses of perfused mesenteric resistance vessels to various contractile agents and peri-arterial nerve stimulation. 2. Fish oil feeding for 4 weeks caused a decrease in the responses to exogenous noradrenaline and electrical nerve stimulations but had no significant effect on vasopressin and KCl (80 mmol/L) induced contractions. 3. These results provide direct evidence for specific attenuation of vascular responses to sympatho-adrenal stimulation in resistance vessels following fish oil feeding and may account for the antihypertensive effects seen in humans and in some forms of hypertension in rats.

Topics: Animals; Body Weight; Dietary Fats, Unsaturated; Electric Stimulation; Fish Oils; Hypertension; Male; Mesenteric Arteries; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Perfusion; Rats; Rats, Inbred SHR; Vascular Resistance; Vasopressins

The demonstration that exogenous atrial natriuretic polypeptide (ANP) has markedly lowered plasma antidiuretic hormone (ADH) suggests a possible negative control of endogenous ANP on the secretion of ADH from the posterior hypophysis. To test this possibility and to clarify the role of ADH and ANP in the pathophysiology of essential hypertension (EHT), the responses of ADH and ANP to a hypertonic saline infusion were investigated in EHT patients and normotensive subjects (NT). Twenty inpatients with EHT (10 males and 10 females; 50.5 +/- 6.5y) and 10 NT subjects (5 males and 5 females; 50.6 +/- 7.8y) underwent a 20 min intravenous infusion of hypertonic saline (2.5% NaCl; 0.25ml/kg/min) in a fasting state. Blood samples were drawn before and 10, 20, 30, 45 and 60 min after the infusion and analyzed for ADH and ANP as well as plasma osmolarity (Posm), Na and albumin. Basal levels of ADH and ANP were not significantly different between NT and EHT. ADH was rapidly increased by the infusion in both groups; however, its percent increase was much higher in EHT than in NT during and after the infusion. Surprisingly, a highly significant negative correlation between ADH and ANP was found before and after the infusion in both groups. Although blood pressure was not changed significantly, the enhanced response of ADH to a sodium and volume load may play a role in part in the pathophysiology of EHT. In addition, it has been suggested that a possible suppression by ANP on the secretion of ADH may be one of the mechanisms of the diuretic action of ANP.

Topics: Adult; Atrial Natriuretic Factor; Female; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Osmolar Concentration; Saline Solution, Hypertonic; Serum Albumin; Sodium; Vasopressins

Several recent reports have suggested that pressor hormones may be released during and after carotid endarterectomy and that release of these factors may be associated with postoperative hypertension and other postoperative morbidity. We measured vasopressin, adrenocorticotropic hormone, and cortisol in jugular venous blood during carotid endarterectomy under general anesthesia in 43 patients with routine carotid shunting. Jugular venous vasopressin increased significantly after the second period of carotid occlusion for shunt removal and remained increased at closure. Vasopressin did not change during the initial carotid occlusion for shunt placement or during the endarterectomy itself, and neither ACTH nor cortisol changed at any sample time. Greater resting vasopressin and cortisol and larger responses of vasopressin were observed in patients receiving phenylephrine to correct intraoperative hypotension. There were no correlations between postoperative hypertension or postoperative complications and intraoperative hormone values. These results suggest (1) basal intraoperative vasopressin values reflect the blood volume of the patient, (2) increased vasopressin was not related to postoperative morbidity, and (3) intraoperative increases in pressor hormones are most likely physiologic responses to specific stimuli such as hypovolemia or hypotension rather than pathologic phenomena. We speculate that the increase of vasopressin after the second carotid occlusion and reperfusion of the brain may be due to the action of humoral factors released into the carotid circulation from the endarterectomy site.

Topics: Aged; Analysis of Variance; Brain; Endarterectomy, Carotid; Female; Humans; Hydrocortisone; Hypertension; Hypotension; Jugular Veins; Male; Middle Aged; Pressoreceptors; Reperfusion; Vasopressins

The mechanisms of anti-hypertensive effect of diuretics remain unknown. The purpose of this study was to test the hypothesis that long-term treatment with chlorthalidone decreases the responsiveness of resistance vessels to neurohormones. The study was performed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats with and without treatment with chlorthalidone (Chlor. 8 mg/day, for 20 days). Resting mean arterial pressure in freely moving state was significantly reduced in DOCA-salt-Chlor rats when compared to DOCA-salt rats (116 +/- 3 vs 147 +/- 7 mmHg, respectively). Chlorthalidone treatment reduced the high plasma sodium content observed in DOCA-salt rats to the same levels observed in normotensive control groups. Results obtained in isolated perfused mesenteric arteries showed: a) the increase in perfusion pressure elicited by norepinephrine (NE), serotonin (SE) and vasopressin (VP) was significantly greater in DOCA-salt than in DOCA-salt + Chlor rats or control normotensive rats; b) the endothelium removal increased the pressor responses to NE, SE and VP in a similar way in all groups. These data provide evidence that long-term chlorthalidone treatment reduces vascular hyperresponsiveness to these neurohormones. In addition, these results indicate that this reduction in vascular hyperresponsiveness, associated with a decrease in extracellular sodium level, could be a possible mechanism by which the diuretics reduce the high blood pressure.

Topics: Animals; Blood Pressure; Chlorthalidone; Desoxycorticosterone; Hypertension; In Vitro Techniques; Male; Mesenteric Arteries; Norepinephrine; Rats; Rats, Inbred Strains; Serotonin; Sodium; Vascular Resistance; Vasoconstriction; Vasopressins

The influence of chronic saline drinking and/or DOCA-salt treatment on plasma renin activity and renal renin concentration was studied in vasopressin-deficient homozygous (DI) Brattleboro rats and their vasopressin-secreting heterozygous (non-DI) littermates. The activity of renin-angiotensin system (RAS) can be suppressed even in the absence of vasopressin under the conditions of a sufficiently high salt intake that is achieved in DI rats by consumption of 0.6% saline instead of water. An almost complete RAS suppression in both plasma and kidney was observed in young animals in which high salt intake induced not only blood volume expansion but also blood pressure elevation, i.e. in mildly hypertensive unilaterally nephrectomized saline drinking DI rats as well as in moderately hypertensive DOCA-salt treated DI rats and in non-DI rats with a severe DOCA-salt hypertension. Our results indicate that intravascular expansion and blood pressure changes are important factors for the modulation of plasma and renal renin activity even in the absence of vasopressin.

Topics: Animals; Blood Pressure; Blood Volume; Desoxycorticosterone; Extracellular Space; Female; Hypertension; Kidney; Rats; Rats, Brattleboro; Renin; Renin-Angiotensin System; Sodium, Dietary; Vasopressins

Behavioral stress and high dietary salt have been reported to increase blood pressure additively in non-human primates. This study was designed to replicate this phenomenon and to assess neuroendocrine correlates and responses to two commonly used antihypertensives, a beta-adrenoceptor blocker and a thiazide diuretic. High-salt intake (240 mmol sodium per day) and stress were administered for 9 weeks in adult baboons. Oral atenolol hydrochloride (50 mg, twice daily) or hydrochlorothiazide (25 mg/day) was administered for 2 weeks each. In all four baboons, salt loading and stress increased systolic blood pressure (SBP) chronically by 14 mmHg, with increases in water intake, urine osmolality and excretion of sodium, decreases in levels of serum sodium, plasma renin activity and plasma vasopressin and no changes in urinary excretion of norepinephrine or epinephrine. Neither drug decreased SBP during ongoing high salt and stress. The results confirm the additive chronic effects of high-dietary salt intake and behavioral stress on blood pressure in non-human primates. The hypertension in this model is resistant to two antihypertensive drugs commonly used clinically.

Topics: Animals; Atenolol; Atrial Natriuretic Factor; Creatinine; Dopamine; Epinephrine; Hydrochlorothiazide; Hydrocortisone; Hypertension; Male; Norepinephrine; Osmolar Concentration; Papio; Renin; Sodium; Sodium, Dietary; Stress, Physiological; Vasopressins

We have recently shown that changes in blood sodium concentration within the limited range of +/- 15 mmol/l induce changes in blood pressure which are directly related to intracellular sodium concentration and inversely related to the transmembrane sodium gradient. It followed from this that the blood pressure response to an incremental change in blood sodium concentration induced by an intraperitoneal salt load should be a function of the rate of accumulation of cell sodium. This was tested in rats treated with deoxycorticosterone acetate (DOCA)-saline for 3 days since at this time cell permeability to sodium is known to be increased. The rise of cell sodium when blood sodium concentration, measured 30 min after loading, ranged from 140-160 mmol/l, was significantly increased in treated animals (0.14 versus 0.21 mmol/kg dry weight for each 1 mmol/l rise in extracellular sodium concentration) and the rise in blood pressure was correspondingly greater (0.81 versus 1.43 mmHg for a 1 mmol/l rise in extracellular sodium concentration). The increased accumulation of cell sodium was not accompanied by a similar increase in water, so that the rise in intracellular sodium concentration was also exaggerated. Prior uninephrectomy slowed the excretion of the salt load sufficiently to exaggerate the rise of blood sodium concentration in response to a given load. The osmotic effects of intraperitoneal high sodium or high sucrose were both equally reduced, indicating that the increased permeability induced by DOCA is not specific for sodium but affects non-electrolytes as well; thus, it probably involves the phospholipid matrix.

Topics: Animals; Blood Volume; Cell Membrane Permeability; Desoxycorticosterone; Hypertension; Male; Muscle, Smooth, Vascular; Osmolar Concentration; Rats; Rats, Inbred Strains; Sodium, Dietary; Sucrose; Vasopressins

In six patients with essential hypertension (EH) and in six healthy volunteers (C) the effects of a 60-min intravenous (iv) infusion of human atrial natriuretic peptide (alpha-hANP) (24 ng/min/kg) on systemic and renal hemodynamics and renal excretory function were evaluated. Basal plasma ANP concentrations in patients with EH were higher (P less than .05) than in C (30.9 +/- 4.5 v14.0 +/- 1.7 pmol/L). Maximal effects of alpha-hANP infusion occurred after 30 to 60 min. Blood pressure (BP) declined from 154 +/- 5/109 +/- 4 to 139 +/- 7/94 +/- 4 in EH and from 117 +/- 1/72 +/- 2 to 106 +/- 1/65 +/- 3 mm Hg in C (P less than .05). Cardiac output (CO) increased transiently from 6.1 +/- 0.3 to 6.5 +/- 0.4 L/min in EH and from 6.8 +/- 0.3 to 7.2 +/- 0.5 L/min in C, whereas heart rate (HR) remained constant both in patients with EH and in C (69 +/- 3 to 72 +/- 5 and 60 +/- 3 to 63 +/- 3/min). The increases in urine flow and in urinary sodium excretion from 3.6 +/- 0.2 to 16.0 +/- 2.0 mL/min and from 230 +/- 33 to 1004 +/- 137 mumol/min, respectively, in EH were more pronounced than in C (from 3.9 +/- 1.0 to 8.4 +/- 0.8 mL/min and from 211 +/- 37 to 451 +/- 84 mumol/min); (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Cyclic GMP; Glomerular Filtration Rate; Heart Rate; Hemodynamics; Humans; Hypertension; Infusions, Intravenous; Kidney; Male; Regional Blood Flow; Renin; Sodium; Vasopressins

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.

Topics: Animals; Blood Pressure; Body Weight; Catecholamines; Deamino Arginine Vasopressin; Drinking; Ganglionic Blockers; Heart Rate; Hexamethonium Compounds; Hypertension; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sympathetic Nervous System; Vasopressins

The effects of lifetime captopril treatment on vasopressin (VP) were assessed in spontaneously hypertensive rats (SHR). Pregnant and nursing dams were treated with oral Captopril (100 mg/kg/day). After weaning, the pups were maintained on Captopril (50/kg/day) for 19-20 wks. Blood pressures of Captopril-treated SHR were in the normotensive range and significantly lower (p less than .001) than SHR control rats. Control and Captopril-treated SHR were perfused and brains were sectioned for immunohistochemical staining with a polyclonal antibody directed against vasopressin (VP). Compared to control SHR, Captopril-treated rats displayed decreased VP-like immunoreactivity in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Captopril treatment also selectively decreased the number of brightly labeled cell bodies in the SON and PVN and reduced VP-like labeling in the axons of the neurons in these nuclei. Concurrent with a decrease in VP-like immunoreactivity, Captopril treatment reduced plasma VP levels (RIA) (p less than 0.01, Captopril, 5.6 +/- 0.5 pg/ml; control, 11.8 +/- 2.2 pg/ml). Scatchard analysis of 3H-VP binding indicated that Captopril treatment increased the number but not the affinity of VP receptors in the hypothalamus and brain stem of SHR. These results suggest that in SHR oral Captopril treatment attenuates the synthesis and release of VP, an effect that may contribute to the blood pressure lowering effect of converting enzyme inhibitors.

Topics: Animals; Brain; Captopril; Female; Humans; Hypertension; Immunohistochemistry; Male; Rats; Rats, Inbred SHR; Vasopressins

Topics: Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Nitroprusside; Osmolar Concentration; Vasopressins

Vasopressin plasma concentrations have been measured in two groups of subjects, 13 moderate essential hypertensive patients without target organ damage and eight control normotensive subjects, before and after the assumption of the upright position, and intravenous infusions of hypotonic saline (0.45% NaCl, 0.25 ml kg-1 min-1 for 1 h) and hypertonic saline (100 mmol NaCl in 50 ml). Plasma vasopressin in recumbent baseline conditions was not significantly different in the two groups. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels, which were not significantly different between the two groups. Plasma renin activity increased in the upright position, was reduced by administration of hypotonic saline and unaffected by hypertonic saline, with no differences between the hypertensives and normotensives. After hypertonic saline, urinary flow rate and urinary sodium excretion in the hypertensive group increased to values significantly (p less than 0.05) higher than in normotensive subjects. In conclusion our study excludes significant alteration of vasopressin regulation in moderate uncomplicated hypertension. In hypertensives although the response of vasopressin to an osmotic load is preserved, the data suggest that the renal handling of the osmotic load may be altered.

Topics: Adult; Aged; Blood Cell Count; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Posture; Renin; Saline Solution, Hypertonic; Sodium; Vasopressins

This study examined the contribution of the main pressor systems to the residual hypertension exhibited by genetically hypertensive (LH) rats of the Lyon strain after early chronic sympathectomy with guanethidine. Blood pressure (BP) was recorded in conscious LH and normotensive control (LN) rats, either intact or sympathectomized, during sequential blockade of the renin-angiotensin system, vasopressin receptors, the autonomic nervous system, and finally after maximal vasodilation with hydralazine. In sympathectomized rats 1) renin-angiotensin system blockade equally reduced BP in both strains, whether it was realized before (-20%) or after (-30%) vasopressin antagonism; 2) isolated vasopressin antagonism decreased BP in LH (-8%) but not in LN rats; 3) autonomic blockade and hydralazine induced additional decreases in BP that were similar in both strains; and 4) intermediate and final levels of BP remained always higher in LH than in LN rats. It is concluded that, after sympathectomy, BP is maintained primarily by the renin-angiotensin system. In sympathectomized LH rats, the maintenance of hypertension does not depend on hyperactivity of the main pressor systems but rather on an increase in the intrinsic vascular resistance that develops in the absence of the sympathetic innervation of the vessels.

Topics: Angiotensin I; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Guanethidine; Hypertension; Male; Rats; Rats, Mutant Strains; Receptors, Vasopressin; Renin; Renin-Angiotensin System; Sympathectomy, Chemical; Vasopressins

In previous studies we found that vasopressin stimulation of both cyclic AMP (cAMP) formation in cortical collecting tubules (CCT) and sodium reabsorption in isolated perfused kidneys was markedly exaggerated in rats with mineralocorticoid hypertension. In the present study, we tested the response (cAMP accumulation) of cortical and outer medullary collecting tubules (OMCT) to vasopressin in two rat models that are resistant to deoxycorticosterone acetate (DOCA)-induced hypertension, the Wistar-Furth strain and NaCl-deficient rats. The blood pressure of normal outbred Wistar rats rose to hypertensive levels (systolic pressure more than 165 mm Hg) during a 5-week treatment with DOCA (10 mg/week) and 1% saline to drink. Significant hypertrophy of the heart and kidneys was also observed. Vasopressin (10(-8) M)-induced cAMP formation was enhanced 3.4-fold in the CCT (OMCT unchanged) of hypertensive rats compared with normotensive controls. Significant hypertrophy (as indexed by tubule diameter) of the CCT but not the OMCT was also observed in DOCA-salt hypertensive rats. Restriction of dietary NaCl (0.13% in chow, tap water to drink) completely prevented DOCA-induced hypertension, organ and CCT hypertrophy, and enhancement of vasopressin-stimulated cAMP formation in the CCT. In Wistar-Furth rats, DOCA-salt treatment did not alter blood pressure or cause significant organ hypertrophy. However, DOCA-salt treatment enhanced vasopressin-stimulated cAMP formation by 4.1-fold in CCT of Wistar-Furth rats, with significant tubular hypertrophy in the CCT but not the OMCT. We conclude that DOCA-induced hypertension and changes in CCT function are dependent on excess dietary NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Cyclic AMP; Desoxycorticosterone; Hypertension; Hypertrophy; Kidney Tubules, Collecting; Male; Rats; Rats, Inbred WF; Sodium, Dietary; Vasopressins

Data about direct effect of vasopressin (VP) on the central arterial pressure (AP) orientated us to investigate the effect of its local administration in the median eminence (ME) of the hypothalamus in rats. For this purpose VP was administered in ME under micropellet form. AP was measured indirectly on the tail of rats up to 96th hour after operation. After implantation of VP there was an elevation of AP with maximum in the first hour, which was statistically significant (p less than 0.01). Identical manipulation (sham operation) was performed to control the lesion effect. Transitory lowering of AP with maximum in the first hour was also established and it was statistically significant (p less than 0.001), For exclusion a nonspecific systemic effect of VP the same dose was administered in the parietal cortex, during which transitory and short-lasting reaction occurred in the first hour after the operation. The data indicate that the peptide, administered in ME under micropellet form, could induce a longlasting hypertensive effect.

Topics: Animals; Blood Pressure; Drug Implants; Hypertension; Male; Median Eminence; Rats; Time Factors; Vasopressins

When cultured in the presence of fetal calf serum, arterial smooth muscle cells from spontaneously hypertensive rats (SHR) proliferate more rapidly and are more numerous at confluency than cells from normotensive Wistar-Kyoto (WKY) animals. The phenomenon has been demonstrated in several laboratories but its molecular origin remains unclear. On the other hand phospholipase C activation and c-fos transcription are early events able to trigger cell mitosis. Therefore, the enhancement of inositol phosphates formation induced in SHR cells by various vasoactive agents and growth factors suggests that this enzyme might be implicated in the abnormal proliferation triggered by serum. In this case a unique molecular abnormality would be responsible for both arterial hypercontractility and dystrophy encountered in hypertension. In order to test this hypothesis we have compared DNA replication, phospholipase C activation, and c-jun and c-fos nuclear protooncogene transcriptions stimulated by fetal calf serum (FCS), vasoactive agents (angiotensin II and vasopressin), and epithelial growth factor (EGF) in SHR and WKY rat cells. The results obtained with these various agonists tested under the same experimental conditions confirm that the classical pathogenic diagram: (PLC hyperactivation----increase in c-fos transcription----enhanced cell proliferation) may apply to the action of vasoactive agents which are only slightly mitogenic on SHR cells, but not to the very important effect of fetal calf serum. Indeed, FCS stimulated inositol phosphate formation and c-jun and c-fos transcription, but none of these parameters was enhanced in SHR cells. Phospholipase C activation may exert some control upon DNA replication, as its partial inhibition by pertussis toxin coincided with an equivalent decrease in thymidine incorporation. It is, however, not absolutely required for the onset of DNA replication in aortic smooth muscle cells, as shown by the results obtained with EGF under the same experimental conditions. An abnormal molecular reaction different from PLC activation is therefore responsible for the enhanced proliferation of cultured SHR aortic smooth muscle cells, and several cell alterations may concur to the formation of the hypertensive arteriopathy.

Topics: Angiotensin II; Animals; Aorta; Cell Division; Cells, Cultured; DNA; DNA Replication; Enzyme Activation; Epidermal Growth Factor; Gene Expression; Hypertension; Muscle, Smooth, Vascular; Oncogenes; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Thymidine; Transcription, Genetic; Type C Phospholipases; Vasopressins

The role of the hypothalamus (HTH) in the pathogenesis of genetic hypertension was studied in spontaneously hypertensive rats (SHR). It is currently believed that, in this strain, the genetic defect manifests itself mainly in the HTH. We examined this hypothesis by grafting HTH neurons from embryos of SHR or control Wistar Kyoto (WKY) rats into the HTH of adult normotensive WKY rats. Changes in host systolic blood pressure (SBP) were monitored, and alterations in vasoactive intestinal polypeptide (VIP) gene expression of the host brain were studied. In rats grafted with HTH tissue from SHR embryos (G-SHR), the blood pressure rose by 31% as compared with that in the grafted control group. The blood pressure climbed gradually over a period of 6 weeks to its highest level, which was maintained for at least 3 months following grafting. Along with the elevated blood pressure, the heart weight increased by 80% compared to controls. Behavioral changes were also evident in the G-SHR rats, and these were similar to those of the native SHR strain. In situ hybridization histochemistry showed a 40% elevation in VIP transcripts in the suprachiasmatic nucleus of the host G-SHR brain compared to controls. These studies demonstrate that transplantation of embryonic SHR HTH tissue into brains of adult normotensive rats results in the development of hypertensive characteristics in the host. It thus appears that the HTH is a prime candidate for the source of changes leading to spontaneous hypertension in mammals.

Topics: Animals; Blood Pressure; Brain Tissue Transplantation; Fetal Tissue Transplantation; Hypertension; Hypothalamus; Immunohistochemistry; Myocardium; Neurons; Nucleic Acid Hybridization; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Vasoactive Intestinal Peptide; Vasopressins

To elucidate the contributions of renal, humoral, and arterial baroreceptor reflex components to salt-induced hypertension, we administered 10% NaCl intravenously for 10 days to sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7), sinoaortic-denervated rabbits with intact kidneys (n = 7), and sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy (n = 7). Serial changes in mean arterial pressure (MAP), heart rate, and blood pressure variability were recorded. In sinoaortic-denervated rabbits with unilateral nephrectomy, MAP increased significantly from 109 +/- 2 to 124 +/- 3 mm Hg (day 4) and remained elevated for the rest of the experiment. This elevation of MAP was accompanied by a reduction in the standard deviation of MAP, with significant elevations in plasma vasopressin, norepinephrine, and atrial natriuretic peptide concentrations and in sodium retention. In the other groups, there were no significant changes in these vasoactive hormones. In the sham-operated sinoaortic-denervated rabbits with unilateral nephrectomy, sodium retention was similar to that of sinoaortic-denervated rabbits with unilateral nephrectomy. Continuous infusion (1 microgram/kg/hr) of a V1 antagonist prevented the elevation of blood pressure and plasma norepinephrine, the accumulation of sodium, and the reduction of blood pressure lability, whereas a bolus injection (10 micrograms/kg) on day 4 reduced blood pressure from 128 +/- 3 to 115 +/- 2 mm Hg (p less than 0.005). These results imply that vasopressin plays a crucial role in the expression of salt-induced hypertension in rabbits with compromised baroreceptor and renal function.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Denervation; Endocrine Glands; Female; Heart; Heart Rate; Hypertension; Nephrectomy; Pressoreceptors; Pressure; Rabbits; Sodium; Sodium Chloride; Vasopressins

It has been shown that after parathyroid hormone (PTG) administration vasopressin increases the falling rate of the renal cortical blood flow and decreases the falling rate of the renal medullary blood flow in normotensive rats. In spontaneously hypertensive rats (SHR) the PTG decreases the falling rate of the cortical and medullary blood flow after vasopressin administration. PTG-induced hypercalcemia in SHR followed by vasopressin administration leads to the renal blood flow redistribution reaction due to which the medullary blood flow dominates over the cortical one.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Drug Interactions; Hypertension; Kidney Cortex; Kidney Medulla; Parathyroid Hormone; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Renal Circulation; Vasopressins

Intracerebroventricular administration of serotonin (5-HT) to conscious rats increases mean arterial pressure (MAP) and decreases heart rate. To determine the mechanisms involved, 5-HT (2.5 micrograms) was injected intracerebroventricularly into conscious rats pretreated with various neurotransmitter and hormone antagonists. The selective 5-HT2 antagonist LY 53857 abolished the increase in MAP and the bradycardia elicited by 5-HT. The increase in MAP produced by 5-HT was potentiated by chlorisondamine (a ganglionic antagonist), unaffected by prazosin (an alpha 1-antagonist) or a vasopressin V1 antagonist alone, but eliminated by the combined pretreatment with prazosin plus the vasopressin antagonist. In contrast, the bradycardia was eliminated by either the vasopressin V1 antagonist or chlorisondamine. In conclusion, 5-HT injected into the lateral cerebral ventricle of conscious rats induces sympathoexcitation and the release of vasopressin, which results in an increase in MAP; 5-HT also elicits a bradycardia mediated through an interaction of the autonomic nervous system with circulating vasopressin.

Topics: Animals; Autonomic Nervous System; Blood Pressure; Bradycardia; Chlorisondamine; Ergolines; Heart Rate; Hypertension; Injections, Intraventricular; Male; Prazosin; Rats; Rats, Inbred Strains; Serotonin; Serotonin Antagonists; Vasopressins

To investigate the interaction of cardiac glycosides with vasoconstrictors, we examined the effects of short term treatment with the cardiac glycoside digoxin (6 mg/kg/day, i.p., for 6 days) in rats made hypertensive by chronic infusion of norepinephrine (NE), angiotensin II (A II) or vasopressin (VP). When digoxin was administered simultaneously with NE at 1.8 mg/kg/day (i.p.) by use of osmotic minipumps in conscious rats, systolic blood pressure decreased to 120 +/- 3 mmHg on Day 1 whereas it rose to 148 +/- 2 mmHg in rats given NE alone (p less than 0.01). The antihypertensive effect of digoxin was sustained for the entire experimental period and was not associated with any change in urinary sodium excretion. When the same dose of digoxin was administered simultaneously with A II at 900 micrograms/kg/day (i.p.) in conscious rats, systolic blood pressure rose to a greater extent than in those given A II alone. The administration of digoxin had no effect on the blood pressure elevation induced by chronic infusion of VP at a rate of 7.2 U/kg/day (i.p.). It is concluded that short term treatment with digoxin has a variety of effects on blood pressure in rats; pressor, depressor, or is no effects depending upon vasoconstrictor used.

Topics: Angiotensin II; Animals; Blood Pressure; Digoxin; Drug Interactions; Hypertension; Natriuresis; Norepinephrine; Rats; Rats, Inbred Strains; Vasopressins

Early chronic sympathectomy does not normalize blood pressure (BP) in genetically hypertensive rats of the Lyon strain (LH). The purpose of this study was to examine the role of the renin angiotensin system (RAS) and vasopressin in the residual hypertension exhibited by LH sympathectomized rats. Chronic sympathectomy was achieved by treating male LH and control normotensive LN rats with guanethidine sulfate between 1 and 13 weeks of age (60 mg/kg daily from day 7 after birth to day 25, 30 mg/kg daily from day 26 to day 70 and 30 mg/kg every other day from day 71 to day 90). At 14 weeks of age, catheters were inserted into the lower abdominal aorta and inferior vena cava via the left femoral artery and vein. After 2 days of recovery, BP was continuously recorded in the conscious freely moving animals during 3 consecutive 1-hour periods: before and after administration of either an angiotensin converting enzyme inhibitor (perindopril 2 mg/kg i.v.) or a selective vascular vasopressin antagonist [beta-mercapto- beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2, Arg8-vasopressin, AVPX 10 micrograms/kg i.v.) and finally after conjoint administration of both drugs. At the end of each period, the efficacy of blockade was verified by the disappearance of pressor responses to respective agonists (angiotensin I 150 ng/kg i.v., Arg8-vasopressin 10 ng/kg i.v.). Chronic treatment with guanethidine resulted in the disappearance of pressor responses to tyramine (250 micrograms/kg i.v.) indicating complete functional denervation of the vessels. Under basal conditions, the 1-hour average value of mean BP (MBP) was higher in LH than in LN sympathectomized rats (134 +/- 3 vs 104 +/- 2 mmHg, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antihypertensive Agents; Blood Pressure; Guanethidine; Hypertension; Indoles; Male; Perindopril; Rats; Renin-Angiotensin System; Sympathectomy, Chemical; Tyramine; Vasopressins

The purpose of this study was to examine pressor hormones and platelet alpha 2-adrenergic receptors in elderly unmedicated free-living subjects. Eighty-seven subjects, 70 +/- 5 years old (mean +/- SD), hypertensive or normotensive (blood pressure less than 160/90 mm Hg) were recruited for measurement of blood levels of norepinephrine, epinephrine, and vasopressin, as well as density and affinity of alpha 2-adrenergic receptors from platelet membranes, assessed by maximal binding (Bmax) and dissociation constant (Kd) of rauwolscine. They were separated into white hypertensive (n = 22) or normotensive (n = 41), and black hypertensive (n = 11) or normotensive (n = 13) groups, with similar age distribution throughout and similar blood pressure levels in the hypertensive and normotensive groups. Vasopressin was higher in the black hypertensive than white hypertensive group (1.5 +/- 1.0 vs. 0.7 +/- 0.5 pg/ml, respectively, p less than 0.005), whereas epinephrine correlated inversely with diastolic blood pressure (r = -0.7, p less than 0.02, in the black hypertensive group). Kd was higher in the black normotensive group than in the other groups (1.6 +/- 0.6 vs. 1.0 +/- 0.2, 1.1 +/- 0.3, or 1.0 +/- 0.3 nM in the white normotensive, black hypertensive, or white hypertensive group, respectively, p less than 0.002). Bmax was no different among groups but was significantly correlated with vasopressin levels for the whole group (r = 0.4, p less than 0.0004) although no such correlation existed within the black hypertensive group. The data suggest that various vasoconstrictor systems participate to different extents in the mechanisms generating and sustaining hypertension in elderly white and black subjects.

Topics: Aged; Black People; Blood Platelets; Female; Humans; Hypertension; Male; Norepinephrine; Receptors, Adrenergic, alpha; Vasopressins; White People

Vascular responsiveness was evaluated in perfused mesenteric arteries from rats infused with dexamethasone (2 micrograms/day). Full dose-response curves to noradrenaline, vasopressin and potassium chloride were established. In order to investigate whether prostaglandins or noradrenaline uptake were involved in dexamethasone-induced pressor changes, vascular responses were compared before and during treatment with either indomethacin (a cyclo-oxygenase inhibitor) or desipramine (an inhibitor of neuronal catecholamine uptake). Dexamethasone-treated tissues showed an increased vascular sensitivity to noradrenaline compared with controls; the maximal response was greater and the concentrations of agonist required for a 50% response (EC50) was less in dexamethasone-treated tissues. The responses to vasopressin and potassium chloride were not affected. Systolic blood pressure in dexamethasone-treated rats was not significantly different from that in controls. Indomethacin infusion decreased the vascular responsiveness to noradrenaline in control and dexamethasone-treated rats to a similar degree. Noradrenaline responses after indomethacin treatment were not significantly different in control and dexamethasone-treated tissues. 6-Keto-prostaglandin-F1 alpha output during stimulation with noradrenaline was not affected by dexamethasone. Desipramine lowered pressor responses to noradrenaline at all concentrations and decreased the maximal response in tissues from dexamethasone-treated but not control rats. However, during infusion with desipramine, the EC50 for noradrenaline after dexamethasone was still less than in controls. Dexamethasone at low doses appears to selectively increase vascular sensitivity to noradrenaline in rats at a prehypertensive stage by changing prostaglandin synthesis and, possibly, neuronal uptake of noradrenaline.

Topics: Animals; Blood Pressure; Desipramine; Dexamethasone; Dose-Response Relationship, Drug; Hypertension; Indomethacin; Male; Mesenteric Arteries; Norepinephrine; Potassium Chloride; Rats; Rats, Inbred Strains; Vascular Resistance; Vasopressins

Urinary digoxin-like factor, ADH, sodium and potassium excretion and urine osmolality were studied during the development of two pathogenically different models of hypertension, DOCA-salt (low-renin) and Gold-blatt 2 kidney-1 clip (renin-dependent). Urinary digoxin-like factor was increased in rats that were given saline (NaCl 1%) to drink, uninephrectomized-salt and DOCA-salt rats, with no significant differences between the two groups urinary ADH was elevated in DOCA-salt rats during the study, compared with uninephrectomized-salt rats. Urinary digoxin-like factor and urinary ADH were not significantly modified in Goldblatt 2 kidney-1 clip and sham-operated rats. In addition, positive correlations between digoxin-like factor urinary excretion and urinary ADH and also with sodium urinary excretion were found. These data suggest that: a) digoxin-like factor and ADH could play a role in the pathogenesis of DOCA-salt but not in Goldblatt 2 kidney-1 clip hypertension. b) A common mechanism may stimulate ADH and digoxin-like factor simultaneously. c) Digoxin-like factor plays a role in the control of urinary sodium excretion.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Hypertension; Hypertension, Renovascular; Male; Natriuretic Agents; Potassium; Rats; Rats, Inbred Strains; Renin; Sodium; Vasopressins

Blood pressure and selected putatively influential hormones were measured in Brattleboro rats which were without diabetes insipidus and which were subjected to various manipulations in dietary sodium intake. Rats fed a control diet from weaning to 16 weeks of age showed a slow increase in blood pressure whereas rats fed a sodium-enriched diet for the same period exhibited sustained hypertension (115 +/- 3 versus 169 +/- 5 (S.E.M.) mmHg). In animals fed a sodium-enriched diet plasma concentrations of antidiuretic hormone (ADH) were significantly increased from 55 +/- 8 to 108 +/- 5 fmol/l. Rats fed the control diet from weaning (group A) and subsequently maintained on that diet or changed to a sodium-enriched diet or sodium-deficient diet showed no differences in their blood pressure. Plasma hormone concentrations were similar in these groups, with the exception of aldosterone suppression in rats switched from control to a sodium-enriched diet (0.26 +/- 0.04 versus 0.08 +/- 0.03 nmol/l; P less than 0.001). Animals fed the sodium-enriched diet from weaning to 16 weeks of age (group b) and either maintained on that diet or changed to a control diet showed little change in their established hypertension. Transfer to the control diet was associated with increased plasma renin concentrations (PRC) (13.8 +/- 2.1 to 122.6 +/- 6.2 nmol/l) and plasma aldosterone concentrations (0.04 +/- 0.01 to 0.08 +/- 0.01 nmol/l; P less than 0.001) but corticosteroids and ADH concentrations were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Animals; Cortisone; Desoxycorticosterone; Diet; Hydroxycorticosteroids; Hypertension; Male; Rats; Rats, Brattleboro; Renin; Renin-Angiotensin System; Sodium, Dietary; Vasopressins

Renal function was evaluated in normal and after 30 days of 5/6 renal mass reduction (CRF) in Munich-Wistar (MW) rats, spontaneously hypertensive rats with superficial glomeruli (EPM), and in Brattleboro rats with congenital diabetes insipidus (DI). Mean arterial pressure was higher in EPM-Control and EPM-CRF rats as compared with MW and DI rats. MW and EPM rats with CRF showed increases of 120% and 196%, respectively, in single nephron glomerular filtration rate as compared with their controls. However, DI rats with CRF did not show any increase in single nephron glomerular filtration rate as compared with the control group. Therefore, the data suggest that the presence of hypertension enhances the adaptive mechanisms on remnant kidney's function. Conversely, in the absence of antidiuretic hormone, adaptive mechanisms of remnant nephrons did not occur. In addition, it was observed that rats with CRF submitted to prostaglandin blockade with indomethacin showed for MW rats a 55% and 20% reduction in ultrafiltration coefficient and in single nephron glomerular filtration rate, respectively. Decreases of 60% and 30% in ultrafiltration coefficient and single nephron glomerular filtration rate, respectively, were observed for EPM rats. In contrast, DI rats did not show any alteration on renal function after indomethacin. It seems, therefore, that prostaglandins play a role in remnant nephron function of MW and EPM rats, but in the absence of antidiuretic hormone, prostaglandins do not affect remnant glomerular hemodynamics.

Topics: Animals; Blood Pressure; Diabetes Insipidus; Glomerular Filtration Rate; Hypertension; Kidney Failure, Chronic; Kidney Glomerulus; Male; Nephrectomy; Nephrons; Prostaglandins; Rats; Rats, Inbred Strains; Vasopressins

We evaluated the antihypertensive mechanism of enalapril, a long-lasting inhibitor of angiotensin-converting enzyme, in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The hypertensive effect of norepinephrine (1.8 mg/kg/day intraperitoneal (i.p.] or vasopressin (7.2 U/kg/day i.p.) was completely abolished by simultaneous administration of enalapril (6 mg/kg/day i.p.). The antihypertensive effect of enalapril was not reversed by simultaneous administration of subpressor doses of angiotensin II (36 and 100 micrograms/kg/day i.p.). However, the hypertensive effects of angiotensin II at pressor doses (600 and 900 micrograms/kg/day i.p.) in enalapril-infused rats were not different from those in vehicle-infused rats. These results indicate that the hypotensive effect of enalapril may in part depend on a reduced sensitivity of the vasculature to norepinephrine and vasopressin, independent of inhibition of angiotensin II formation.

Topics: Angiotensin II; Animals; Drug Therapy, Combination; Enalapril; Hypertension; Injections, Intraperitoneal; Male; Norepinephrine; Rats; Rats, Inbred Strains; Vasopressins

In the past several years, investigators have given evidence that vasopressin (VP), in addition to its antidiuretic function, may play an important role in cardiovascular regulation through other mechanisms. An increased plasma VP level has been reported in some patients with mild-to-moderate essential hypertension (EH). Additionally, yohimbine, a selective alpha 2-adrenoceptor antagonist, has been shown to increase the plasma VP level and blood pressure (BP) in man. The present study was performed to evaluate the effects of chronically administered guanfacine, a centrally acting alpha 2-adrenoceptor agonist, on high plasma VP levels in patients with mild-to-moderate EH in whom no other causes responsible for elevated plasma VP levels were present. The relations among VP, BP and renin-angiotensin-aldosterone system were also investigated. Eleven patients (8 women and 3 men aged 62 +/- 3 years) with untreated and uncomplicated EH were included in the study after a 2-week placebo period and kept on a diet containing 120 mmol sodium and 80 mmol potassium daily. In all patients treated once daily with 1 mg of guanfacine for 4 weeks, the drug-induced changes in plasma levels of VP and aldosterone (ALD), plasma renin activity (PRA), plasma osmolality, BP and heart rate were determined. A marked reduction in plasma VP levels (p less than 0.001) was observed and this was accompanied by a significant fall in mean arterial blood pressure (p less than 0.001). No significant changes in heart rate, plasma osmolality, PRA and plasma ALD levels were found. The results suggest that guanfacine might suppress VP secretion via alpha 2-adrenoceptors without significantly affecting renin-angiotensin-aldosterone system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Blood Pressure; Female; Guanfacine; Guanidines; Humans; Hypertension; Male; Middle Aged; Osmolar Concentration; Phenylacetates; Renin; Vasopressins

A rare case with Guillain-Barré syndrome complicated by inappropriate secretion of antidiuretic hormone (SIADH) and hypertension was reported. This case showed clinically mild symptoms without respiratory muscle paralysis and had a complete neurological recovery. It should, therefore, be considered that the Guillain-Barré syndrome may cause SIADH and hypertension independent of the severity of the disease.

Topics: Child; Epinephrine; Humans; Hypertension; Inappropriate ADH Syndrome; Male; Neurologic Examination; Norepinephrine; Polyradiculoneuropathy; Renin-Angiotensin System; Sodium; Sympathetic Nervous System; Vagus Nerve; Vasopressins

Cardiovascular and hormonal responses to aortic cross-clamping (ACC) and declamping (ADC) were studied in 20 patients undergoing reconstructive aortic surgery anesthetized with fentanyl and droperidol. Ten of the patients served as a control group, and 10 patients were treated with oral captopril (25 mg the day before operation and 25 mg one hour before anesthesia) to prevent intraoperative and postoperative hypertension. After the induction of anesthesia in the captopril group, hypotension was seen in four patients and bradycardia in three patients. In both groups, the most important changes in hemodynamics after the ACC were an increase in systemic vascular resistance and decreases in cardiac and stroke index. After the ADC, the cardiac index (CI) improved nearly to the level before the ACC. The urine output during anesthesia was 46 +/- 5 mL/h in the control group and 73 +/- 11 mL/h (P less than 0.05) in the captopril group. Postoperatively, patients in both groups were hypertensive and tachycardic. In the control group, plasma renin activity rose significantly during the ACC, indicating activation of the renin-angiotensin system (RAS). In both groups, significant increases in plasma vasopressin (PAVP), epinephrine, and norepinephrine were also observed before the ACC and during the postoperative period. The results suggest that oral captopril increases the risk of hypotension and bradycardia after induction of anesthesia, and does not prevent postoperative hypertension.

Topics: Adult; Aorta, Abdominal; Blood Pressure; Captopril; Cardiac Output; Catecholamines; Central Venous Pressure; Constriction; Heart Rate; Hemodynamics; Humans; Hypertension; Middle Aged; Premedication; Pulmonary Wedge Pressure; Renin; Stroke Volume; Urine; Vascular Resistance; Vasopressins

The endocrine (plasma renin activity, insulin and ADH) and hemodynamic responses (heart rate and mean arterial pressure) to isoprenaline infusion were examined in conscious deoxycorticosterone-salt hypertensive rats (DS) and compared with uninephrectomized-salt control rats (US). A dose-related rise in plasma renin activity and plasma insulin values was found in US rats, while no change in either parameter was observed in DS rats after 30 min of isoprenaline infusion. ADH was not increased in US rats at any dose of isoprenaline infusion. However, in DS rats the largest dose (450 ng/kg/min) produced a significant rise. Isoprenaline infusion increased the heart rate in both groups, but the increases in the DS group were significantly lower than in the US group for the 200-ng/kg/min dose (p less than 0.01). The drop in mean arterial pressure was found to be more pronounced in DS rats than in US rats at 50, 100 and 200-ng/kg/min isoprenaline doses. Recovery of the mean arterial pressure to basal levels was also found in US rats with the various doses of isoprenaline administered. However, in DS rats the different doses of isoprenaline produced a progressive drop in mean arterial pressure with no recovery at the end of 30 min of isoprenaline infusion. The present results provide no evidence of subsensitivity to isoprenaline in the resistance vessels of conscious DS rats and suggest that the greater hypotensive response observed in these rats may be due to the inability of the renin-angiotensin system to adequately compensate the vasodilation produced by isoprenaline.

Topics: Animals; Desoxycorticosterone; Endocrine Glands; Hemodynamics; Hypertension; Insulin; Isoproterenol; Male; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Renin; Vasopressins

To assess the mechanism by which inhibitors of angiotensin converting enzyme (ACE) lower blood pressure, we evaluated the role of endogenous angiotensin II in the antihypertensive effect of MK 421, a long-lasting ACE inhibitor, in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The hypertensive effect of norepinephrine (1.8 mg/kg/day, ip) or vasopressin (7.2 U/kg/day, ip) was inhibited by the simultaneous administration of MK 421 (6 mg/kg/day, ip). Additional administration of angiotensin II at a subpressor dose (36 micrograms/kg/day, ip) did not revert the antihypertensive effect of MK 421 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of ACE inhibitors may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that the suppressed angiotensin II may not be essential for the antihypertensive effect of ACE inhibitors in rats made hypertensive by chronic infusion of norepinephrine or vasopressin.

Topics: Angiotensin II; Animals; Blood Pressure; Enalapril; Hypertension; Male; Norepinephrine; Rats; Rats, Inbred Strains; Reference Values; Vasopressins

A study was made of the effect of a single intake of captopril on the neurohumoral mechanisms of the regulation of renal circulation in 25 patients with essential hypertension (EH). Captopril induced an increase of the effective renal blood flow (ERB) and of the effective renal plasma flow along with a considerable lowering of the renal vascular resistance. No relationship was found between these changes and the time course of changes in the activity of plasma renin, aldosterone and vasopressin concentration in blood plasma. The relationship was established between the changes in the ERB and the time course of changes in baroreceptor sensitivity that significantly increased in the majority of EH patients under the effect of captopril.

Topics: Adult; Captopril; Drug Evaluation; Hemodynamics; Humans; Hypertension; Iodohippuric Acid; Middle Aged; Neurotransmitter Agents; Radionuclide Imaging; Renal Circulation; Renin-Angiotensin System; Vasopressins

The role of vasopressin (AVP) and angiotensin II (ANG II) in the onset of acute (45 min) aortic coarctation hypertension was studied in conscious rats. Changes in mean carotid pressure (MCP) and heart rate (HR) were measured in four groups of rats. Control rats presented a hypertensive response that attained a plateau 5 min after coarctation and remained near this level throughout the experiment. Rats treated with AVP V1-vascular receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5Tyr(Me)AVP] presented a prompt rise in MCP similar to the control rats, but in contrast to this group, the MCP started to decline progressively. Rats treated with saralasin presented a delay in the onset of hypertension right after coarctation but slowly attained values similar to those for control rats. In contrast, the rats treated with AVP antagonist plus saralasin showed a blunted MCP elevation throughout the experiment. Reflex bradycardia observed in the rats treated with saralasin or the AVP antagonist plus saralasin was similar to that observed in the control rats, whereas for the group treated only with AVP antagonist, the reflex bradycardia was more intense than for the other three groups, indicating an increased sensitivity of the baroreflex. These data demonstrate that in addition to the mechanical effect of aortic constriction, both ANG II and AVP participate in the onset of acute aortic coarctation hypertension. Moreover, the results indicate that ANG II acts on the prompt (5 min) rise in pressure, whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation.

Topics: Acute Disease; Angiotensin II; Animals; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Carotid Arteries; Heart Rate; Hypertension; Male; Rats; Rats, Inbred Strains; Saralasin; Vasopressins

Topics: Animals; Blood Pressure; Humans; Hypertension; Rats; Rats, Inbred SHR; Vasoconstriction; Vasopressins

Hypertonic saline (100 mmol in 50 ml) was injected intravenously over 5 min in two groups of moderate essential hypertensive patients (group 1, n = 13; group 2, n = 6). In group 2, arterial pressure had been lowered by infusion of clonidine (0.3 mg in 100 ml saline), from 186 +/- 8/116 +/- 3 to 146 +/- 9/98 +/- 5 mmHg (mean +/- s.e.m.). The hypertonic stimulus increased the plasma osmolality of all subjects from 288 +/- 1 to 296 +/- 1 mosmol/kg (P less than 0.01). Plasma vasopressin increased from baseline values that were not significantly different (P less than 0.01) in each of the two groups. The increase in plasma vasopressin was significantly greater (P less than 0.05) in the group 2 hypertensives with a reduced arterial pressure (+7.81 +/- 1.79 pg/ml) than in the group 1 untreated hypertensives (+3.15 +/- 1.2 pg/ml). In our study, acute lowering of arterial pressure by clonidine did not significantly change baseline vasopressin, but facilitated osmotically induced vasopressin secretion.

Topics: Blood Pressure; Clonidine; Drug Evaluation; Female; Humans; Hypertension; Infusions, Intravenous; Male; Middle Aged; Time Factors; Vasopressins; Water-Electrolyte Balance

The role of vasopressin in the regulation of body water volume and its distribution to intravascular, interstitial and intracellular compartments, and the importance of particular body water compartments in the pathogenesis of DOCA-salt hypertension were studied in young Brattleboro rats. Vasopressin-deficient, vasopressin-synthesizing and vasopressin-deficient rats chronically supplemented with deamino-8-D-arginine vasopressin (dDAVP) were compared with water-drinking controls. The chronic DOCA-salt treatment caused a marked hypertension in vasopressin-synthesizing animals; in these animals body water was slightly increased due to the expansion of extra-cellular fluid volume whereas intracellular water tended to decrease, so that the ratio of extracellular fluid volume to intracellular water rose significantly. The development of DOCA-salt hypertension was attenuated in the vasopressin-deficient rats, which had a similar level of total body water, slightly increased intracellular water and significantly decreased extracellular fluid volume compared with the hypertensive vasopressin-synthesizing rats. Consequently, in the vasopressin-deficient rats, the ratio of extracellular fluid volume to intracellular water did not differ from that of controls. A vasopressin deficiency was associated with a failure to expand the interstitial fluid volume although plasma volume was increased. Unaltered total body water together with elevated plasma osmolality indicated an extracellular water deficiency in DOCA-salt-treated vasopressin-deficient rats. Chronic dDAVP supplementation restored the body fluid pattern and the hypertensive response of the DOCA-salt-treated vasopressin-deficient rats. In conclusion, the antidiuretic effects of vasopressin are necessary for the interstitial fluid volume expansion that is essential for a full development of DOCA-salt hypertension.

Topics: Animals; Body Water; Chronic Disease; Deamino Arginine Vasopressin; Desoxycorticosterone; Heterozygote; Homozygote; Hypertension; Nephrectomy; Rats; Rats, Brattleboro; Sodium Chloride; Vasopressins

We have previously reported an increased urinary excretion of vasopressin without a rise in circulating levels of this hormone in the deoxycorticosterone acetate (DOCA)-hypertensive pig (DH). The present study was designed to characterize the renal handling of vasopressin in DH that might account for this paradox. DOCA hypertension was produced in seven domestic female pigs by means of subcutaneous implants of Silastic rubber impregnated with DOCA. Thirty days after DOCA implantation, urinary clearances of inulin, para-aminohippurate (PAH), and vasopressin were measured in the conscious animals during infusion of a 5% dextrose solution, first without and then with lysine vasopressin. Subsequent to this study, four of the pigs were placed on a low-sodium (10 meq/kg food) diet for 4 wk. At the end of this period, the clearances were again evaluated. We observed an increased urinary vasopressin clearance (CLVP) in the DH associated with an increased urinary flow but without significant changes in the clearances of inulin or PAH. Dietary sodium restrictions reversed the hypertension and the increased urinary flow and returned the CLVP to normotensive levels. These results indicate that the increased urinary excretion of vasopressin in DH is because of an increased urinary clearance of this hormone. This increased urinary CLVP is the consequence of the high urine flow in these pigs.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Female; Glomerular Filtration Rate; Hypertension; Lypressin; Reference Values; Renal Circulation; Renin; Sodium; Swine; Vasopressins

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Topics: Animals; Arginine Vasopressin; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Bradycardia; Carbachol; Cardiovascular Physiological Phenomena; Cardiovascular System; Deamino Arginine Vasopressin; Hypertension; Injections, Intraventricular; Male; Nicotine; Parasympatholytics; Phentolamine; Physostigmine; Rats; Rats, Brattleboro; Vasopressins

The area postrema is a circumventricular organ that plays an important role in neurohumoral regulation of the circulation. We have developed a method to examine permeability and vascular responses of the microcirculation of the area postrema in vivo. A craniotomy was performed over the dorsal brain stem in anesthetized rats, and blood vessels to the area postrema were visualized with fluorescein microscopy. Extravasation of sodium fluorescein (MW, 386), but not 150 kDa (MW) fluorescein isothiocyanate-dextran, occurred in the area postrema under control conditions. There was no extravasation of fluorescein or dextran in the brain stem under control conditions. Acute hypertension produced marked disruption of the barrier to 150 kDa dextran in the area postrema, compared with minimal disruption in the brain stem. We tested the hypothesis that the area postrema has greater permeability to small molecules than the brain stem and that this permeability might be accompanied by distinctive vascular responses. Topical suffusion of adenosine and ADP produced similar dose-related dilation of arterioles to area postrema and dorsal brain stem. Topical and intravenous vasopressin produced similar dose-related constriction of vessels to area postrema and brain stem. Electron microscopy in rats demonstrated that a barrier to horseradish peroxidase, which is absent in capillaries in the area postrema, is present in arterioles that supply the area postrema.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Arabinose; Arterioles; Blood Vessels; Capillary Permeability; Cerebral Ventricles; Horseradish Peroxidase; Hypertension; Male; Microcirculation; Osmolar Concentration; Rats; Rats, Inbred Strains; Vasoconstriction; Vasopressins

Following our previous report that development of DOC-salt hypertension is attenuated in female rats, we have now determined the effects of gonadectomy on the pathogenesis of this model of hypertension. Male and female rats were gonadectomized at age three weeks, and the DOC-salt protocol was initiated two weeks later and continued for three weeks. In intact rats, hypertension developed more rapidly and to a higher level in males than in females. By contrast, in gonadectomized rats, there was no sex difference in blood pressure because the development of hypertension was attenuated in males and exacerbated in females. None of these differences could be attributed to differences in either saline consumption or vasopressin release since no differences were found among the groups for either variable. Although the underlying mechanisms are uncertain, our results clearly show that the gonadal hormones affect the development of DOC-salt hypertension in the rat.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Female; Hypertension; Male; Orchiectomy; Ovariectomy; Rats; Rats, Inbred Strains; Sex Characteristics; Sodium Chloride; Vasopressins

Pressor responses to vasopressin were determined in pigs and sheep during three experimental periods: 1) before deoxycorticosterone acetate (DOCA) treatment, 2) 21 days after DOCA implantation (100 mg/kg) when a stable hypertension had developed, and 3) after reversal of the hypertension by removing the implant in the sheep or by decreasing the dietary sodium intake in the pigs. The infusion of lysine (LVP) or arginine (AVP) vasopressin into pigs and sheep, respectively, resulted in dose-dependent increases in plasma vasopressin concentration. The levels of plasma LVP or AVP achieved by these infusions were not altered in any of the experimental periods. The administration of vasopressin resulted in dose-dependent increases in mean arterial blood pressure. However, pigs required five times more LVP than sheep required AVP to achieve similar pressor responses. The pressor responsiveness to vasopressin was attenuated when either species was made hypertensive. This effect was reversed when normal blood pressure was restored by reducing sodium intake in the pigs or by removing the DOCA implant from the sheep. These data establish that an increased pressor response to vasopressin does not contribute to DOCA hypertension in pigs or sheep.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Female; Hypertension; Lypressin; Male; Sheep; Swine; Vasopressins

Four physiological mechanisms are known to be important for recovery of arterial pressure (AP) after acute hemorrhage. These are the sino-aortic baroreflex (SA), the vagally mediated cardiopulmonary baroreflex (CP), the renin-angiotensin system (RA), and the vasopressin system (VP). We evaluated in anesthetized rabbits the relative importance of these mechanisms by repeating rapid, 10% arterial hemorrhage (6.5 ml/kg) once before and once after eliminating one of them and comparing the posthemorrhage hypotension. The study was conducted in two series. In the first series, we randomly grouped 24 rabbits into four groups, i.e., a sinoaortic baroreceptor-denervated group (SA) a vagotomized group (CP), a renin-angiotensin-blocked group (RA), and a vasopressin-blocked group (VP). In control conditions, AP fell to 88% at 2 min and 92% at 6 min after completing the hemorrhage. Significantly greater hypotension (e.g., 74% at 6 min) occurred only in the SA group. In the second series, we randomly classified 18 rabbits into three groups, i.e., an autonomic ganglion-blocked group (AB) plus a RA group and a VP group as before. Hypotension significantly greater than control (68% opposed to 91% at 6 min) occurred only in the AB group. We submit that as far as restoration of arterial pressure after rapid, mild hemorrhage in the rabbit is concerned, the arterial baroreceptor reflex system plays a far more important role than the vagally mediated cardiopulmonary baroreflex, the vasopressin system, or the renin-angiotensin system triggered directly by a fall in renal arterial pressure.

Topics: Animals; Autonomic Nerve Block; Heart Rate; Hemorrhage; Hypertension; Pressoreceptors; Rabbits; Reflex; Renin-Angiotensin System; Vagotomy; Vasopressins

The role of antidiuretic and pressor effects of vasopressin (VP) in deoxycorticosterone acetate (DOCA)-salt hypertension was studied in young and adult Brattleboro rats. The antidiuretic VP action was a necessary prerequisite for the development of severe DOCA-salt hypertension. The insufficient expansion of extracellular fluid volume in DOCA-salt-treated VP-deficient (DI) rats was associated with the attenuation of their hypertensive response, although they had highly increased blood volume and extracellular sodium. Chronic [deamino]-D-arginine vasopressin supplementation that restored volume and distribution of body fluids in DI rats permitted the full development of DOCA-salt hypertension. Blood pressure response to DOCA-salt treatment was always greater in young than in adult Brattleboro rats (even in animals lacking pressor or both VP effects). In animals in which antidiuretic VP effects were present, the pattern of body fluid response to DOCA-salt treatment was also age dependent. There was a tendency to intravascular expansion in young hypertensive rats, whereas an increase of interstitial fluid volume was found in adult animals. The elimination of VP pressor action lowered systemic resistance much more in adult than in young hypertensive rats. We conclude that 1) in adult but not in young rats antidiuretic VP effects are essential for the occurrence of blood pressure response to DOCA-salt treatment, 2) the restoration of body fluids due to antidiuretic VP action enables the development of hypertension in both age groups of DI rats, and 3) pressor VP effects contribute to the maintenance of hypertension, especially in adult animals.

Topics: Aging; Animals; Blood Pressure; Blood Volume; Cardiac Output; Desoxycorticosterone; Diuresis; Female; Hypertension; Rats; Rats, Brattleboro; Vascular Resistance; Vasopressins

To investigate the central nervous system (CNS) changes in the spontaneously hypertensive rat (SHR), a tissue culture model was used to examine the content and release (24 hour) of the peptide hormones, vasopressin (VP) and oxytocin (OT), from brain explants. Nuclear regions consisting of the paraventricular (PVN) or supraoptic (SON) nuclei were microdissected from prehypertensive SHR and Wistar-Kyoto (WKY) rats. Media levels of VP and OT were measured at 1, 3, 4, and 7 days of culture. After three days of culture, the PVN explants from SHR secreted significantly less VP and OT (both reduced 80%) than did those from WKY. Release of both VP and OT in the SON explants was significantly lower (approximately 50% lower) in the SHR only at seven days of culture. Additionally, tissue content of the peptides was measured after 0, 1, 4, and 7 days of culture. Tissue content of VP and OT was decreased (40% or more) in the SHR in both nuclear regions after four and seven days of culture. In addition, nicotine was found to stimulate the release of VP from SON, but not PVN, cultures in both SHR and WKY explants. Immunohistochemical data showed that there was not a preferential loss of VP or OT neurons in explants from the SHR. Therefore, this in vitro model would indicate that there is a difference in the ability of cultured explants of PVN and SON from SHR and WKY (four-week-old) to synthesize and/or release the peptide hormones VP and OT.

Topics: Animals; Culture Techniques; Hypertension; Immunohistochemistry; Male; Nicotine; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Supraoptic Nucleus; Vasopressins

In a search for factors contributing to the sustained blood pressure (BP) elevation in acutely volume-loaded animals, dextran dissolved in lactated Ringer's solution (20 ml/kg) was infused into 34 mongrel dogs over a period of 1 hour under pentobarbital anesthesia and changes in hemodynamic and humoral variables were monitored during its infusion and for 3 hours after its infusion. BP elevation during volume loading (from 114 +/- 3 to 128 +/- 3 [SEM] mm Hg) was attributed to an increase in cardiac output. After volume loading, some dogs maintained BP elevation whereas others did not. The former group showed an increase in total peripheral resistance, demonstrating a transformation of cardiac output to total peripheral resistance as a responsible factor in maintenance of the elevated BP. The plasma levels of norepinephrine, vasopressin, and plasma renin activity were not elevated, indicating that these vasoactive factors were not responsible for elevation of the BP or total peripheral resistance. The changes in the hematocrit, atrial natriuretic factor, urine volume, and urinary sodium excretion were identical in the two groups, and natriuresis was not prominent when total peripheral resistance was high. Pressor responses to norepinephrine and angiotensin II were potentiated 3 hours after stopping infusion in both groups, but this potentiation was not correlated with the increase in total peripheral resistance or mean BP. Thus, acute volume expansion produced resistance-dependent hypertension following the initial volume-dependent hypertension. It is unlikely that a vascular sensitizing natriuretic factor plays a role in the resistance-dependent BP elevation. The mechanism and physiological importance of hypersensitivity to vasoactive substances remain to be elucidated.

Topics: Aldosterone; Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Volume; Cardiac Output; Dextrans; Dogs; Epinephrine; Heart Rate; Hypertension; Natriuresis; Norepinephrine; Renin; Vascular Resistance; Vasoconstriction; Vasopressins

The purpose of this study was to determine the effect of chronic blockade of the brain renin-angiotensin system on the hormonal response to stress in spontaneously hypertensive rats (SHR). To this end, we measured changes in plasma corticosterone, vasopressin, plasma renin activity, aldosterone, norepinephrine, and epinephrine in SHR treated with a 4-week intracerebroventricular infusion of captopril (osmotic minipump, 1.25 micrograms/hr) or vehicle in response to cold stress (4 degrees C x 4 hours) or ether stress (5 minutes). Within the fourth week of treatment, the average systolic blood pressure of captopril-treated SHR was significantly lower than that of vehicle-treated rats. Basal plasma levels of corticosterone, but not vasopressin, were significantly lower in SHR treated with captopril. In response to cold stress, captopril-treated SHR showed significantly lesser increases in both corticosterone and vasopressin than did vehicle-treated SHR. There were no differences in basal plasma levels of norepinephrine, epinephrine, plasma renin activity, or aldosterone between captopril-treated and vehicle-treated SHR, and both groups showed elevations of a similar magnitude after exposure to cold. In response to ether stress, captopril-treated SHR also showed significantly smaller increases in corticosterone and vasopressin than did vehicle-treated SHR. These results suggest that chronic intracerebroventricular administration of captopril, through blockade of the brain renin-angiotensin system, alters the hormonal response of SHR to stress.

Topics: Adrenocorticotropic Hormone; Angiotensin II; Animals; Blood Pressure; Captopril; Corticosterone; Hypertension; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Renin-Angiotensin System; Stress, Physiological; Vasopressins

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Hypertension; Receptors, Angiotensin; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Receptors, Vasopressin; Vasopressins

Platelet activation factor (PAF)-, ADP and vasopressin-induced increments of platelet Ca2+ concentration were measured by quin-2 in 64 patients with essential hypertension and 16 normal donors. Basal concentration of free Ca2+ was 87 +/- 4 nM in donors, 106 +/- 5 nM in patients with labile hypertension (LH) and 122 +/- 6 nM in those with stable hypertension (SH) (p less than 0.01). PAF, ADP and vasopressin, added to platelets, increased [Ca]in by 448 +/- 58, 397 +/- 66, and 277 +/- 50 nM, respectively, in the donors, by 473 +/- 57, 479 +/- 54 and 195 +/- 32 nM, in LH patients, and by 607 +/- 85, 584 +/- 73 and 245 +/- 41 nM in SH patients. There were no significant variations between the three samples, using the ANOVA test. In 20 patients, whose both parents had essential hypertension, [Ca]in increment was 738 +/- 8 nM for PAF, 682 +/- 90 nM for ADP, and 320 +/- 61 nM for vasopressin. In 19 patients, who admitted to no essential hypertension in the family, these parameters were significantly lower: 310 +/- 40 nM for PAF, 389 +/- 61 nM for ADP, and 147 +/- 26 nM for vasopressin. The demonstrated changes may be making an important contribution to the maintenance of elevated vascular tone and provide an evidence in favor of a genetically-predetermined EH variety.

Topics: Adenosine Diphosphate; Adult; Blood Platelets; Calcium; Cytoplasm; Humans; Hypertension; Male; Middle Aged; Platelet Activating Factor; Receptors, Cell Surface; Vasopressins

In two experiments, binding sites for atrial natriuretic factor (ANF) were studied in discrete areas of rat brain by quantitative autoradiography. In the first experiment, the maximum binding capacity of 125I-ANF was reduced significantly in the subfornical organ and choroid plexus of 4 and 14 week old spontaneously hypertensive (SHR) rats compared to aged-matched Wistar-Kyoto (WKY) normotensive controls. In contrast, the maximum binding capacity of 125I-ANF in the area postrema was similar for young and adult SHR and WKY rats. The second experiment involved a comparison of brain ANF binding sites in Long-Evans control rats and Brattleboro rats with inherited diabetes insipidus. The maximum binding capacity of 125I-ANF was significantly greater in the subfornical organ of Brattleboro rats compared to Long-Evans controls. However, no strain differences occurred for 125I-ANF binding in the choroid plexus or area postrema. These findings indicate that the number of ANF binding sites in discrete areas of rat brain may be influenced in a highly selective fashion by alterations in body fluid homeostasis (i.e., hypertension or diabetes insipidus). Changes in brain ANF binding sites within circumventricular areas may involve central as well as peripheral sources of ANF-related peptides.

Topics: Aging; Animals; Atrial Natriuretic Factor; Autoradiography; Brain; Diabetes Insipidus; Disease Models, Animal; Hypertension; Male; Neuropeptides; Rats; Rats, Brattleboro; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Atrial Natriuretic Factor; Vasopressins

The cardiovascular responses to selective alpha 1- and alpha 2-adrenoceptor antagonism (with prazosin and idazoxan, respectively) were assessed in rats 4 weeks after unilateral nephro-adrenalectomy, contralateral adrenal enucleation and the provision of a 1% NaCl solution as drinking fluid (AEN rats) and in sham-operated (SON) rats. Measurements were made between 0700 and 1000 h and between 1400 and 1700 h, since we have previously shown that resting blood pressures (BPs) in AEN rats are higher in the morning than in the afternoon. Following prazosin administration (morning or afternoon), BP fell to similar levels in both SON and AEN rats. Idazoxan, given 20 min after the start of prazosin infusion, caused similar transient falls in BP in all four groups of rats. Following the subsequent additional antagonism of angiotensin II (Ang II) production (with captopril) and vasopressin (V1) receptors [with d(CH2)5DAVP], BP in AEN rats studied in the morning was higher than in SON rats at that time of day, and higher than in AEN rats studied in the afternoon. These findings suggest than an additional underlying mechanism capable of increasing BP exists in AEN rats studied in the morning.

Topics: Adrenal Glands; Adrenalectomy; Adrenergic alpha-Antagonists; Animals; Blood Pressure; Circadian Rhythm; Dioxanes; Hypertension; Idazoxan; Male; Nephrectomy; Prazosin; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Vasopressin; Renin-Angiotensin System; Vasopressins

The purpose of this study was to assess the participation and interaction of the renin-angiotensin system and vasopressin in the early stages of the development of salt-induced hypertension. Subtotally nephrectomized rats, fed 1% saline, were treated over a 10-day period with either an antivasopressor V1 antagonist (by osmotic minipump) or an angiotensin converting enzyme inhibitor (either captopril or ramipril, given daily by oral gavage), or a combination of the two modes of treatment. Surprisingly, only ramipril (either alone or in combination with the V1 antagonist) could prevent the development of hypertension in these animals. Our data would not permit conclusion as to whether the different capacity of these agents to prevent salt-induced hypertension was due to a different degree of penetration into the central nervous system, or to some other property.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bridged Bicyclo Compounds; Hypertension; Male; Nephrectomy; Ramipril; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Sodium, Dietary; Vasopressins

Although abnormalities in the vasopressin system have been reported in spontaneously hypertensive rats (SHR), neither short-term nor long-term administration of the vasopressin antagonist d(CH2)5-Tyr(Me)arginine vasopressin (AVP), which selectively blocks the action of vasopressin on vascular (V1) receptors, altered the course of hypertension in SHR. In the current study, long-term administration of a different vasopressin antagonist, d(CH2)5-D-Tyr(Me)VAVP, to SHR and Wistar-Kyoto rats (WKY) from 4 to 12 weeks of age significantly attenuated the development of systolic hypertension in SHR (p less than 0.05) without altering blood pressure in normotensive WKY. The antagonist was delivered subcutaneously by osmopump at 0.1 microgram/hr. Systolic blood pressure was monitored twice weekly by tail plethysmography beginning at 5 weeks of age. In a second group of SHR, the drug infusion was continued until 18 weeks of age. In this group, the attenuation of systolic hypertension by the drug was extended and became more prominent (p less than 0.007). Resting mean arterial pressure measured by indwelling catheters in the conscious state at 18 weeks of age was significantly reduced in the antagonist-treated SHR (144 +/- 4 vs 157 +/- 4 mm Hg; p less than 0.05). Heart rate also was significantly reduced by the drug (351 +/- 6 vs 392 +/- 7 beats/min; p less than 0.001). Following measurement of mean arterial pressure in the rats at 18 weeks of age, the osmopumps were removed and systolic blood pressure, mean arterial pressure, and heart rate were observed until 22 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Blood Pressure; Heart Rate; Hypertension; Kidney; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Renin; Vasopressins; Water-Electrolyte Balance

Topics: Adult; Aldosterone; Blood Pressure; Humans; Hypertension; Immersion; Mineral Waters; Renin; Vasopressins

In order to determine if the decreased hypothalamic and increased posterior pituitary content of vasopressin (VP) observed previously in spontaneously hypertensive rats (SHR) were a secondary consequence of the hypertension, the effect of preventing the development of hypertension on VP content of the hypothalamoneurohypophyseal system was evaluated. Two methods for preventing the hypertension were used: (1) chronic angiotensin-converting enzyme inhibition (oral captopril, 100 mg/kg/day at 4-12 weeks of age); and (2) intraventricular 6-hydroxydopamine (6-OHDA, 200 micrograms at 4 and 5 weeks of age). Both of these treatments markedly attenuated the increase in systolic blood pressure in SHRs at 5-11 weeks of age. The captopril-treated rats had a significant elevation in serum renin activity at 12 weeks of age indicating the presence of chronic converting enzyme inhibition, and the 6-OHDA-treatment resulted in a depletion of hypothalamic (86%) and brainstem (76%) norepinephrine content. Hypothalamic VP content was reduced in untreated SHRs compared to normotensive Wistar-Kyoto rats (WKYs, P = 0.0015). It was not significantly altered in either strain by the 6-OHDA treatment. Captopril caused a reduction in hypothalamic VP content in both SHRs and WKYs (P less than 0.01). Posterior pituitary VP content was elevated in untreated SHRs compared to WKYs (P less than 0.001), and remained elevated with captopril and 6-OHDA treatments. These data indicate that the abnormalities in VP content in the hypothalamus and posterior pituitary of SHRs are not a response to the hypertension. Therefore, they may represent primary abnormalities in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Brain; Captopril; Catecholamines; Hydroxydopamines; Hypertension; Hypothalamo-Hypophyseal System; Oxidopamine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasopressins

Recent interest has focused on the role of vasopressin (AVP) in blood pressure (BP) regulation. This study was performed to determine if vasopressin has a compensatory pressor role following acute diuresis in both normal rats and in rats with subtotal nephrectomy (SN) or in rats with SN-salt induced hypertension. An inhibitor (AVP-I), specific for the AVP vascular smooth muscle receptor, was administered intravenously to assess the AVP dependency of the BP. Furosemide administration significantly increased plasma AVP levels in all rats. Administration of AVP-I did not change BP in the normal rats with or without prior furosemide administration or in the SN rats without furosemide administration. In contrast, after furosemide administration, AVP-I significantly decreased mean BP in the SN rats. The administration of AVP-I to the SN-salt hypertensive rats, with or without furosemide administration, significantly decreased mean BP. In conclusion, AVP has a compensatory pressor role in SN rats after acute diuresis, with or without salt-induced hypertension, but not in the normal rat.

Topics: Animals; Blood Pressure; Diuresis; Furosemide; Hypertension; Male; Nephrectomy; Rats; Rats, Inbred Strains; Vasopressins

We evaluated whether or not increased sodium (Na) concentrations of cerebrospinal fluid (CSF) and stimulated activities of brain renin-angiotensin system (RAS) contribute to an enhanced hypertension by salt overload in spontaneously hypertensive rats (SHR). Long-term salt loading (1% NaCl solution as drinking fluid) accelerated the development of hypertension in SHR, but did not alter the blood pressure (BP) in normotensive Wistar-Kyoto rats (WKY). CSF Na concentration was elevated in uninephrectomized (Nx) group as compared to that in control SHR, while in WKY CSF Na was not influenced by the treatment. A fall in BP by intravenous AVP antagonist or hexamethonium was greater in salt-loaded SHR than in controls. This hypotensive response to the combined blockade of AVP and SNS correlated with CSF Na in SHR but not in WKY. Plasma concentration of AVP and epinephrine tended to increase in relation to the degree of salt loading in SHR but not in WKY. Pressor responses to intracerebroventricular (ICV) angiotensin II (AII) and NaCl were greater in SHR than in WKY, although these responses were not influenced by chronic salt load in either SHR or WKY. The enhanced hypertensive action of ICV NaCl in SHR was abolished by pretreatment with ICV AII antagonist. Chronic saline drinking enhanced the depressor effect of ICV captopril in SHR but not in WKY. These observations suggest that salt overload in SHR may cause an elevated CSF Na concentration and an enhanced activity of brain RAS, which may increase activity of SNS and release of AVP, resulting in an enhanced development of hypertension.

Topics: Animals; Blood Pressure; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin-Angiotensin System; Sodium; Sodium Chloride; Sympathetic Nervous System; Vasopressins

Topics: Adolescent; Adult; Humans; Hypertension; Hypothalamic Diseases; Middle Aged; Paraventricular Hypothalamic Nucleus; Supraoptic Nucleus; Vasopressins

To study the regulation of hypothalamic vasopressin (VP) and oxytocin (OT) gene expression in relation to the development of hypertension, levels of VP mRNA and OT mRNA were determined in spontaneously hypertensive rats (SHR). Differences in VP and OT mRNA content of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of 4- and 10-week-old SHR and Wistar-Kyoto controls (WKY) were quantitated by dot-blot and Northern blot analysis. VP and OT pituitary content and VP plasma levels were measured by radioimmunoassays. VP mRNA levels were approximately 2-fold and 3-fold higher in the SON and PVN of 4-week-old SHR, respectively, as compared to controls. The OT mRNA levels were approximately 35% lower in both nuclei of the SHR. There was no difference in VP and OT pituitary content between 4-week-old SHR and WKY, but VP plasma levels were higher in SHR. In the 10-week-old SHR VP mRNA levels were still approximately 30-40% higher and the OT mRNA levels were approximately 40% lower in both nuclei when compared to age-matched WKY. Pituitary VP and OT contents were respectively 1.5-fold higher and 20% lower in the 10-week-old SHR than in 10-week-old WKY. VP plasma levels were still elevated in the SHR. The data indicate that in the hypothalamo-neurohypophyseal system of the SHR the VP system is in a higher state of activity, while the OT system is lower in activity.

Topics: Aging; Animals; Blood Pressure; Gene Expression Regulation; Genes; Hypertension; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Pituitary Gland; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; RNA, Messenger; Supraoptic Nucleus; Transcription, Genetic; Vasopressins

Control of cell calcium handling and transport may be abnormal in hypertension. We have studied calcium efflux rates in response to angiotensin II and vasopressin in cultured vascular smooth muscle cells from New Zealand genetically hypertensive rats and normotensive control rats. Calcium efflux with both peptides was time- and concentration-dependent and was significantly greater in cells from the genetically hypertensive rats (P less than 0.001, analysis of variance). In addition, mean +/- s.d. protein content (0.31 +/- 0.01 versus 0.28 +/- 0.02 mg/well, n = 48, P less than 0.001) and calculated total cell calcium (3.63 +/- 0.27 versus 2.86 +/- 0.32 nmol/mg protein, n = 16, P less than 0.005) were greater in genetically hypertensive rat cells. These data are consistent with the presence of abnormal cell calcium dynamics in hypertension in genetically hypertensive rats.

Topics: Angiotensin II; Animals; Calcium; Cells, Cultured; Hypertension; Muscle, Smooth, Vascular; Rats; Rats, Mutant Strains; Saralasin; Vasopressins

This investigation examined the presence and abundance of vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, stroke-prone spontaneously hypertensive rats, and cross-bred diabetes insipidus x stroke-prone spontaneously hypertensive rats. A single-stranded RNA probe complementary to exon C of the vasopressin gene was utilized for in situ hybridization and identified hypothalamic 'vasopressinergic' neurons in tissue from all five strains of rats. The results obtained by solution and in situ hybridization suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous physiological data which suggests cross-bred diabetic-hypertensive rats inherit the mutated vasopressin gene of the Brattleboro rat.

Topics: Animals; Diabetes Insipidus; Hypertension; Male; Rats; Rats, Brattleboro; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transcription, Genetic; Vasopressins

To determine the principal effects of brain angiotensin(Ang) II on the sympathetic nervous system, vasopressin (AVP), and the high and low pressure baroreceptor systems, we observed the hemodynamic and neurohumoral characteristics induced by the acute(1-hr) and chronic(1-wk) infusion of Ang II into the brain ventricle in conscious dogs, and then evaluated the hemodynamic responses to sole-innervated carotid artery occlusion(COR) after Ang II infusion and again after vagotomy in anesthetized dogs. Both acute(50ng/kg/min) and chronic(15ng/kg/min) infusion of Ang II caused a significant rise in arterial pressure without changes in heart rate. Neither acute nor chronic Ang II treatment produced significant changes in plasma renin activity and norepinephrine in plasma and cerebrospinal fluid(CSF), while the plasma and CSF level of AVP was increased in the acute Ang II treatment, but not in the chronic Ang II treatment. The COR was blunted in the acute Ang II treatment compared with those obtained in the chronic Ang II or sham treatment. The blunted pressor response to carotid occlusion in the acute Ang II treatment was restored by cutting the remaining vagus nerve. These results suggest that baroreceptor reflexes are impaired by the acute excess of Ang II in the brain, and it might be mediated through increased vagal afferent activity, changes in the central integration of low and high pressure baroreceptors, and a combination of both.

Topics: Angiotensin II; Animals; Dogs; Hypertension; Injections, Intraventricular; Pressoreceptors; Sympathetic Nervous System; Vagotomy; Vasopressins

The specifics of changes occurring in arterial BP and hemodynamics during a reproduction of various arterial hypertension models were studied in adult and old rabbits. In reproduction of reflexogenic and vasopressor hypertension, the animals revealed irregular changes in electrical activity of hypothalamic nuclei. Age-related differences of changes in the renin-aldosterone system were found. The data obtained suggest that changes of neural and hormonal control associated with ageing promote the development of arterial hypertension in old age.

Topics: Aging; Animals; Blood Pressure; Electrophysiology; Female; Hemodynamics; Hypertension; Hypothalamus; Pregnancy; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Vasopressins

The sensitivity of the vessel smooth muscles to vasopressin and their contractile responses were obviously increased in hypertensive rats, whereas the vasopressin inhibitory effect and tachyphylaxis were decreased. These changes seem to be connected with the prevalence of V1-activating over V2-inhibitory vasopressin receptors in hypertensive rats' vessel smooth muscles. Administration of lithium oxybutyrate for 4 weeks normalized central hemodynamics and decreased the sensitivity to vasopressin. The findings suggest a possible role of the inositol pathway in transmission of hormonal signal (vasopressin) to hypertensive rats' vessel smooth muscles as well as participation of vasopressin in pathogenesis of arterial hypertension and the possibility of using lithium oxybutyrate for its correction.

Topics: Animals; Hemodynamics; Hydroxybutyrates; Hypertension; In Vitro Techniques; Lithium; Muscle Contraction; Muscle, Smooth, Vascular; Organometallic Compounds; Rats; Rats, Inbred SHR; Tachyphylaxis; Vasopressins

In rats with streptozotocin-induced diabetes an increase in arterial blood pressure was observed as early as the first week after the drug was injected. Blood pressure reached maximal values around the fourth week and remained stable for a long period of follow-up. The responsiveness of these rats to the three major vasopressor hormones, angiotensin II, norepinephrine, and vasopressin, was decreased in the early phase of diabetes and returned to normal in the late phase. Acute treatment at the third, sixth, and twelfth weeks with blockers of these vasopressor hormones resulted in a significant fall in blood pressure at the third week with captopril and at the twelfth week with propranolol plus phentolamine. No significant fall was observed when a specific vasopressin inhibitor was administered. Good control of the blood pressure was obtained when these rats were treated chronically with captopril or prazosin, and partial control was achieved when they were fed a low salt diet. An attenuation in arterial blood pressure levels was observed in rats with two-kidney, one clip hypertension when diabetes was induced by streptozotocin. Plasma creatine levels in diabetic rats were significantly higher than those in control rats only in the sixth and twelfth weeks. Electron microscopy revealed some minor glomerular lesions only at the twelfth week.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Humans; Hypertension; Hypertension, Renovascular; Kidney; Norepinephrine; Prazosin; Rats; Time Factors; Vasopressins

Plasmapheresis (PP) was used in 28 patients with medication-resistant high arterial hypertension (AH). PP-induced changes in plasma renin activity and blood aldosterone, angiotensin II and antidiuretic hormone levels of patients with high AH are shown to be a compensatory-adaptive response, maintaining homeostasis. PP sessions (27 ml/kg body weight at a rate of 0.22 ml/kg/min, at the maximum) do not produce renin-angiotensin-aldosterone activation. Long-term hypotensive effect of PP in cases of high AH might be related to a gradual decrease in blood angiotensin II and systemic aldosterone synthesis. It is suggested that the hypotensive effect of PP may be due to an intricate interaction of effects, with humoral, receptor and circulatory re-adjustments of arterial BP control being the most prominent among those.

Topics: Adult; Chronic Disease; Drug Resistance; Female; Humans; Hypertension; Hypertension, Malignant; Male; Middle Aged; Plasmapheresis; Renin-Angiotensin System; Time Factors; Vasopressins

We have investigated the issue of sexual dimorphism in the secretion of vasopressin, its pressor action, and the development of deoxycorticosterone (DOC)-salt hypertension. In normal human subjects on controlled salt intake, the basal secretion of vasopressin, indicated by plasma vasopressin levels and urinary excretion of vasopressin, was higher in men than in women and in blacks than in whites. Basal vasopressin secretion also was higher in male than in female rats. This effect was not associated with a difference in the metabolic clearance of the hormone. The sex-related difference in vasopressin release in rats was abolished by gonadectomy and restored by treatment of males with testosterone and females with ovarian hormones. The pressor responsiveness to vasopressin was higher in male than in randomly cycling female rats. Finally, DOC-salt hypertension, which is dependent on vasopressin, developed more rapidly in male than in female rats. Although there was no sex-related difference in the extent to which plasma vasopressin levels were elevated, pressor responsiveness to vasopressin was greater and baroreflex sensitivity was attenuated to a lesser extent in hypertensive males than in hypertensive females. Thus, it seems likely that gonadal hormones play a significant role in cardiovascular regulation.

Topics: Animals; Black People; Blood Pressure; Desoxycorticosterone; Estrus; Female; Humans; Hypertension; Male; Orchiectomy; Ovariectomy; Rats; Rats, Inbred Strains; Sex Characteristics; Vasopressins; White People

1. The blood pressure lowering and anti-vasoconstrictor effects of BRL 34915 and nifedipine were compared in female spontaneously hypertensive rats (SHR). 2. In conscious SHR, intravenous injection of BRL 34915 (0.1, 0.3 mg kg-1) produced rapid, dose-related falls in mean arterial pressure of greater than 3 h duration. Nifedipine, at the same intravenous dose levels, also evoked rapid anti-hypertensive effects, though these responses were of lesser magnitude and duration than those observed for BRL 34915. 3. In anaesthetized, ganglion-blocked SHR, BRL 34915 (0.1, 0.3 mg kg-1 i.v.) dose-dependently antagonized the pressor responses to incremental intravenous infusions of noradrenaline (3.8-28.5 ng min-1) or phenylephrine (120-907 ng min-1) but did not inhibit pressor responses to incremental infusions of methoxamine (0.47-3.63 micrograms min-1), angiotensin II (7.0-52.9 ng min-1) or vasopressin (0.27-2.0 mu min-1). 4. In anaesthetized, ganglion-blocked SHR, nifedipine (0.1, 0.3 mgkg-1 i.v.) antagonized the pressor responses to each of the infused vasoconstrictor agents, being most effective against responses to noradrenaline or angiotensin II. 5. In pithed SHR, both BRL 34915 and nifedipine (each at 0.3 mg kg-1 i.v.) reduced the basal blood pressure level and produced marked inhibition of frequency-dependent pressor responses evoked by electrical stimulation of the spinal cord sympathetic outflow (0.25-4.0 Hz). Restoration of the basal diastolic blood pressure to within the control range, using a continuous intravenous infusion of vasopressin (0.98 mu min-1), prevented the inhibitory effect of BRL 34915. In the case of nifedipine, however, even raising the basal blood pressure to a level exceeding that recorded in control rats (with vasopressin, 2.0 mu min-1), did not reverse the inhibitory effect of the drug on frequency-dependent pressor responses. 6. It is concluded that the anti-hypertensive properties of BRL 34915 in SHR are probably unrelated to an anti-vasoconstrictor action. In contrast, it is suggested that the broadly-based anti-vasoconstrictor properties of nifedipine may contribute substantially to the anti-hypertensive properties of this drug.

Topics: Angiotensin II; Animals; Benzopyrans; Blood Pressure; Cromakalim; Dose-Response Relationship, Drug; Female; Hypertension; Infusions, Intravenous; Nifedipine; Norepinephrine; Phenylephrine; Pyrroles; Rats; Rats, Inbred SHR; Vasoconstriction; Vasopressins

This study was undertaken to investigate further the possible role of vasopressin in the sexual dimorphism of deoxycorticosterone (DOC)-salt hypertension. The study was carried out 3 weeks after initiating treatment with DOC and salt in uninephrectomized male and female rats. Mean arterial pressure (MAP) was lower in female than in male DOC-salt hypertensive rats (177 +/- 7 versus 198 +/- 4 mmHg; P less than 0.01). Mean arterial pressure did not differ between male and female normotensive control rats. Increases in MAP in response to graded i.v. infusions of vasopressin were markedly attenuated in female normotensive and hypertensive rats, but there was no sex difference in pressor responses to i.v. phenylephrine. Baroreflex sensitivity was reduced in both male and female DOC-salt rats, but to a greater extent in males (P less than 0.01). Diminished pressor responsiveness to vasopressin and a smaller impairment of baroreflex sensitivity may contribute to the reduced development of DOC-salt hypertension in female rats.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Female; Heart Rate; Hypertension; Male; Nitroprusside; Phenylephrine; Pressoreceptors; Rats; Rats, Inbred Strains; Sex Characteristics; Vasopressins

To determine whether angiotensin II (A II) can modify baroreflex centrally and contribute to the central resetting of baroreflex in spontaneously hypertensive rats (SHRs), the aortic depressor nerve (ADN) was electrically stimulated following intracerebroventricular (ICV) administration of A II and/or A II analog in urethane-anesthetized normotensive Wistar rats (WKYs) and SHRs. Electric stimulation of the ADN elicited frequency-dependent depressor, bradycardic, and sympatho-inhibitory responses. Angiotensin II, administered ICV, dose-dependently attenuated these responses induced by ADN stimulation in normotensive rats. We found, however, these attenuations could be abolished by ICV pretreatment with A II analog. Vasopressin (ICV) did not change any responses to ADN stimulation. The vasopressor and sympatho-inhibitory responses to ADN stimulation were significantly less in SHRs when compared with those in WKYs: In SHRs, A II analog completely cancelled the A II-attenuated responses to ADN stimulation. These findings suggest that A II can centrally attenuate baroreflex, which might be independent from vasopressin, and in the brain A II can contribute to the central resetting of baroreflex in SHRs.

Topics: Angiotensin II; Animals; Aorta; Brain; Cardiovascular System; Electric Stimulation; Hypertension; Male; Pressoreceptors; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Reference Values; Reflex; Sympathetic Nervous System; Vasopressins

Inhibition of angiotensin converting enzyme by MK 421 (6 mg/kg/day ip) induced a significant increase in urinary kinin excretion in norepinephrine-infused rats (1.8 mg/kg/day ip), whereas it had no effect on urinary prostaglandin E2 excretion. In contrast, MK 421 did not induced any significant changes in urinary kinin and prostaglandin E2 excretion in vasopressin-infused rats (7.2 U/kg/day ip). The simultaneous administration of indomethacin (10 mg/kg/day sc), OKY 046 (12 mg/kg/day sc) or aprotinin (100,000 units/kg/day sc) did not affect the antihypertensive effect of MK 421 in rats made hypertensive by chronic infusion of norepinephrine or vasopressin. The present results suggest that the hypotensive effect of MK 421 may depend on a reduced sensitivity of the vasculature to vasoconstrictor substances. In addition, it is also suggested that neither the prostaglandin-thromboxane or kallikrein-kinin systems are essential for the antihypertensive effect of MK 421 in these models of hypertension.

Topics: Animals; Aprotinin; Blood Pressure; Enalapril; Hypertension; Indomethacin; Kallikreins; Kinins; Male; Norepinephrine; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxanes; Vasopressins

The major complication of extracorporeal membrane oxygenation (ECMO) for the treatment of neonatal respiratory failure is bleeding related to heparinization. Systolic hypertension has emerged as another serious side effect in our experience. Thirty-eight of the first 41 newborns we treated with ECMO developed a systolic blood pressure greater than 90 mm Hg. The mean hypertension index (HI blood = hours greater than 90/hr on ECMO) was 0.17 +/- 0.16. Possible biochemical mediators were assayed in 17 patients. Plasma renin activity (PRA), aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane, and antidiuretic hormone were elevated. Angiotensin-converting enzyme (ACE) and prostacyclin were not elevated. Eighteen patients (44%) had intracranial hemorrhage (ICH), and 11 patients (27%) had clinically significant ICH. The HI was significantly (p less than 0.005) lower in those patients without ICH (0.11 +/- 0.01) than in those patients with ICH (0.25 +/- 0.04). PRA at hour 12, day 2, and day 3 was significantly higher (p less than 0.05) in patients experiencing ICH (62 +/- 42; 93 +/- 15; 73 +/- 30 ng/ml/hr) than in those without ICH (27 +/- 25; 14 +/- 8; 12 +/- 4 ng/ml/hr). An aggressive approach to medical management evolved that included hydralazine, nitroglycerine, and captopril, which protected against ICH. Two of 23 patients (9%) treated with the protocol sufferred clinically significant ICH, whereas nine of 18 patients (50%) treated before implementation of the protocol experienced ICH. The ACE inhibitor captopril was most effective in the control of hypertension. We conclude that systolic hypertension is common during neonatal ECMO, is associated with ICH, and is related to a high PRA. Aggressive management of hypertension during ECMO can reduce the incidence of ICH, and captopril is an important component of this aggressive medical management.

Topics: Aldosterone; Cardiac Output; Catecholamines; Humans; Hypertension; Infant, Newborn; Oxygenators, Membrane; Peptidyl-Dipeptidase A; Prostaglandins; Renin; Respiratory Insufficiency; Thromboxane B2; Vasopressins

The hypothesis that the vasoconstrictor action of vasopressin may contribute to the development of hypertension in spontaneously hypertensive rats (SHR) was tested by chronic infusion of a specific antagonist of the vascular effects of vasopressin. From 4 to 13 weeks of age, SHR and Wistar-Kyoto rats (WKY) received subcutaneously either isotonic saline or the vasopressin pressor antagonist, d(CH2)5Tyr(Me)arginine vasopressin by osmopump. Systolic blood pressure was measured by tail cuff from 5 to 11 weeks of age. In SHR, the vasopressin analogue did not alter the rate or magnitude of increase in systolic blood pressure. In WKY, systolic blood pressure in the vasopressin analogue group was slightly reduced compared with the saline infusion values until 10 weeks of age (F1, 10 = 10.18, p = 0.008). At 12 to 14 weeks of age, all animals were prepared with indwelling arterial and venous catheters. Resting mean arterial pressure was not altered significantly by the vasopressin analogue infusion in either strain, but the response to an acute vasopressin infusion of 5, 15, or 50 ng/kg body weight was markedly attenuated by the analogue treatment, indicating that plasma levels of the vasopressin analogue were sufficient to block pressor effects of endogenous vasopressin. A bolus injection of the angiotensin II converting enzyme inhibitor teprotide (SQ 20881) resulted in a decrease in mean arterial pressure (p less than 0.05) that was comparable in all groups, and serum renin concentration was not elevated in the vasopressin analogue-treated rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Blood Pressure; Hypertension; Male; Rats; Rats, Inbred SHR; Receptors, Angiotensin; Receptors, Vasopressin; Renin-Angiotensin System; Teprotide; Vasopressins

The age-dependent participation of endogenous vasopressin (VP) during the development of DOCA-salt hypertension was studied in young (28-day-old) and adult (75-day-old) Brattleboro rats. VP-deficient homozygous (DI) rats were compared to heterozygous (non-DI) littermates which do synthetize VP. Six weeks of DOCA-salt treatment did not increase blood pressure (BP) in adult DI rats. On the other hand, in young DI animals there was a significant rise of systolic and mean arterial pressure accompanied by the hypertrophy of the left ventricle. This moderate DOCA-salt hypertension of young DI rats contrasted with severe hypertension of young non-DI rats. Increased BP response of young VP-deficient DOCA-salt treated rats was independent of the saline intake or blood volume expansion which were similar in young hypertensive and adult normotensive DI animals. It could be concluded that vasopressin is not essential for the induction of DOCA-salt hypertension in young rats even if VP is responsible for the magnitude of BP elevation. In contrast to young animals vasopressin is very important for the development of DOCA-salt hypertension in adult rats.

Topics: Aging; Animals; Blood Pressure; Blood Volume; Desoxycorticosterone; Drinking; Drug Synergism; Female; Heterozygote; Homozygote; Hypertension; Kidney; Myocardium; Rats; Rats, Brattleboro; Sodium Chloride; Vasopressins

This study investigated whether excision of either the right or left atrial appendage of rats alters their natriuretic response and the release of atrial natriuretic factor during acute blood volume expansion or reduction. These animals were subjected to a thoracotomy and either had their right or left atrial appendages removed or underwent a right or left atrial sham appendectomy for comparative, control purposes. Intrajugular vein, intracarotid artery, and intravesical catheters were installed 3-4 weeks later under sodium pentobarbital anesthesia. Then, when the rats were conscious, blood volume was expanded using blood from donor rats once every 15 minutes in 3 increments of 10% of the calculated total blood volume at a rate of 5 ml/kg/min. Blood and urine samples were collected before volume expansion and at the end of each 15-minute period, with the withdrawn blood being replaced. A maximal fourfold increase in urinary volume, urinary sodium excretion, and plasma atrial natriuretic factor was observed in all but the right-atrial-appendectomized animals. Plasma atrial natriuretic factor, urinary volume, and urinary sodium excretion were correlated in all 4 groups. No significant changes in blood pressure or hematocrit were noted. Plasma vasopressin, measured at the end of volume expansion, was significantly lower in animals subjected to left atrial appendectomy. High-performance liquid chromatography of plasma from the control groups indicated that most of the released ANF during blood volume expansion corresponded to a high molecular weight peptide. Additional rats, processed as above, were subjected to 10% blood volume decrements.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Blood Pressure; Blood Transfusion; Blood Volume; Disease Models, Animal; Heart Atria; Hemorrhage; Hypertension; Male; Natriuresis; Rats; Rats, Inbred Strains; Sodium; Urodynamics; Vasopressins

An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery or the terminal aorta in deoxycorticosterone acetate (DOCA) hypertensive rats (prepared with DOCA and saline after uninephrectomy) and uninephrectomized control rats. A catheter for pressure measurement was inserted into the terminal aorta through a femoral artery. At rest the carotid and hindquarter (measured at the terminal aorta) blood flows in DOCA hypertensive rats were similar to the respective, corresponding values in normal rats with intact bilateral kidneys. The group mean of superior mesenteric flow was about 70% and that of renal flow about 40% larger than in normal rats. Cardiac output was estimated to be greater in DOCA hypertensive rats than in normal rats. In uninephrectomized control rats, superior mesenteric flow was larger than in normal rats to such an extent that an increase in cardiac output was assumed as in DOCA hypertensive rats, but renal flow was normal (about twice the unilateral renal flow in normal rats). Estimation of regional sympathetic vasoconstrictor tone from the decrease in peripheral resistance with hexamethonium and vasopressin antagonist revealed a substantial tone also in the superior mesenteric and hindquarter areas, where the tone was estimated to be almost absent in normal rats and uninephrectomized rats. It is suggested that hypertension in DOCA hypertensive rats is sustained by an increase in cardiac output and an elevation of vasoconstrictor tone in resistance vessels. Since increase in cardiac output appears to be similarly present in uninephrectomized control rats, the elevation of sympathetic tone due to administration of DOCA and salt seems to be indispensable for DOCA hypertension.

Topics: Animals; Blood Flow Velocity; Blood Pressure; Cardiac Output; Desoxycorticosterone; Hemodynamics; Hypertension; Male; Nephrectomy; Rats; Rats, Inbred Strains; Regional Blood Flow; Renal Circulation; Rheology; Splanchnic Circulation; Vascular Resistance; Vasoconstriction; Vasopressins

1. Plasma concentrations of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured in conscious stroke-prone spontaneously hypertensive (SPR), spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats before and after acute volume expansion or haemorrhage. 2. Plasma ANP concentration was reduced to one-third of resting values 30 min after a 1.5% haemorrhage (1.5 ml of blood per 100 g bodyweight). Plasma ADH concentration rose immediately 50-fold on haemorrhage and remained elevated at 30 min. 3. Plasma ANP concentration increased 2.5-fold relative to resting values 1 min after infusion of 2.0 ml per 100 g 5% dextrose; after 10 min plasma ANP remained elevated. Plasma ADH concentration tended to fall on volume expansion although no significant decrease was observed. 4. There was no difference in the basal levels of ANP and ADH, or in the changes produced by alterations in blood volume, in hypertensive SPR and SHR compared with normotensive WKY. 5. Thus, plasma ANP concentrations moved in opposite directions in response to two physiological stimuli: volume expansion and haemorrhage. Reciprocal changes were observed in plasma ADH.

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Hemorrhage; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Vasopressins

Topics: Adult; Catecholamines; Diet, Sodium-Restricted; Hemodynamics; Humans; Hypertension; Male; Renin; Sympathetic Nervous System; Vasopressins

Abnormalities in the vasopressin and renin systems have been reported in spontaneously hypertensive rats (SHR). Therefore, studies were performed to evaluate the responsiveness of these systems to changes in plasma osmolality and sodium concentration. These variables were manipulated in vivo by intraperitoneal administration of distilled water, isotonic saline, or hypertonic saline to 8- and 18-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Animals were decapitated 30 minutes later, and trunk blood was collected. The hypertonic saline injections resulted in an increase in plasma osmolality and serum sodium at both ages (p less than 0.001). Serum vasopressin was higher in all groups of animals receiving hypertonic saline (1200 mosm/kg H2O; p less than 0.05), but the magnitude of increase was not significantly different in the SHR and WKY at either age. Serum renin activity was lower in SHR than in WKY following acute decreases in serum sodium at 8 weeks, but it was the same for both strains at 18 weeks. Both kidney renin content and concentration were lower in SHR than in WKY at 18 weeks but not at 8 weeks. Therefore, the suppressed renin response to acute osmotic challenge in 8-week-old SHR is not the consequence of reduced kidney renin content. The vasopressin response to osmotic stimulation also was evaluated in vitro using hypothalamoneurohypophyseal explants obtained from 5-, 8-, and 18-week-old SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Age Factors; Animals; Culture Techniques; Hypertension; Hypothalamus; Hypotonic Solutions; Isotonic Solutions; Kidney; Male; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; Saline Solution, Hypertonic; Sodium; Vasopressins

Eleven patients, who had undergone renal transplantation and who had hypertension, aged 19-56 years, were treated with cyclosporine and prednisolone. We measured plasma renin activity, aldosterone and vasopressin (RIAs) at the first, second and third week and again 9 to 12 months after transplantation. Plasma renin activity was in the low-normal range throughout (0.31 +/- 0.05, 0.30 +/- 0.03, 0.32 +/- 0.05 ng/ml/h on short- vs. 0.32 +/- 0.04 ng/ml/h on long-term), aldosterone showed a tendency to decrease (114 +/- 27, 72 +/- 18, 71 +/- 11 pg/ml on short- vs. 54 +/- 23 pg/ml on long-term), whereas vasopressin remained moderately increased during the observation period (10.5 +/- 0.8, 10.4 +/- 1.6, 8.9 +/- 0.6 pg/ml on short- vs. 9.6 +/- 1.0 pg/ml on long-term). We then investigated the reactivity of the renin-system in 5 of the patients by stimulating renin release by captopril. Increases in plasma renin activity were only moderate (0.35 +/- 0.03 vs. 0.66 +/- 0.21 ng/ml/h) and blood pressure dropped only slightly (148 +/- 2.0/98 +/- 1.2 vs. 141 +/- 4.6/95 +/- 4.2 mmHg). Levels of plasma aldosterone were significantly suppressed from a low baseline (46.4 +/- 13.5 vs. 25.3 +/- 6.1 pg/ml, p less than 0.05). The increase in vasopressin was unaffected by captopril (9.6 +/- 1.0 vs. 8.8 +/- 0.4 pg/ml). Our results suggest that in renal transplantation patients with good graft function, the activity of the renin system is unaffected by cyclosporine treatment on short- and on long-term. Vasopressin stimulation does not seem to depend on the renin system and might play a role as a vasoconstrictor in the face of a denervated kidney.

Topics: Adult; Cyclosporins; Female; Humans; Hypertension; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prednisolone; Renin-Angiotensin System; Vasopressins

Vasopressin has been studied intensively in DOCA-salt rats and seems to play an important role in this model of hypertension. In the present study we investigated plasma vasopressin in seven normotensive young volunteers during the early phase of mineralocorticoid-induced hypertension. We administered 0.8 mg/day fludrocortisone for 1 week. Body weight, blood pressure, plasma vasopressin, plasma osmolality and electrolytes, as well as plasma renin activity, were evaluated on days 0, 3 and 7. Blood pressure increased significantly from 117/67 to 121/76 mmHg (P less than 0.05) within 1 week, while plasma osmolality remained unaltered at 284 +/- 3 mOsmol/l. Plasma vasopressin (0.45 +/- 0.1 pg/ml) was increased after 3 days (0.68 +/- 0.5 pg/ml) and rose further to 1.53 +/- 0.27 pg/ml after 1 week (P less than 0.05). Changes in plasma vasopressin concentration were not correlated with alterations in blood pressure. Our results show an increase in plasma vasopressin in the early phase of mineralocorticoid-induced hypertension in man. However, the observed increase is moderate and does not seem to explain the increase in blood pressure alone, but could contribute to the blood pressure increase during mineralocorticoid treatment.

Topics: Adult; Body Weight; Fludrocortisone; Humans; Hypertension; Male; Osmolar Concentration; Renin; Sodium; Vasopressins

The role of the antidiuretic hormone (ADH) in the development and maintenance of the hypertensive state produced by deoxycorticosterone (DOC) and salt in rats is a matter of controversy. The effects of neural lobe lesions that would prevent the release of the hormone to the systemic circulation without affecting the hypothetical release from the hypothalamic nuclei to other areas of the central nervous system was tested. A diabetes insipidus-like syndrome was obtained. But, neither the delay in the onset nor the development of DOC-salt hypertension was modified. This lesion made in rats at 3-4 weeks post DOC-salt did not alter the hypertension during the following 3 more weeks of treatment. These results suggest that the neural lobe would not be essential for the development and maintenance of DOC-salt hypertension in rats.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Hypertension; Male; Pituitary Gland, Posterior; Rats; Vasopressins

Effects of physostigmine on heart rate, mean arterial pressure (MAP), plasma renin concentration (PRC) and vasopressin (AVP) release were investigated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Physostigmine (100 micrograms/kg, i.a.) produced a greater and prolonged hypertensive response in the SHR than in the WKY. Heart rate was increased by physostigmine in SHR rats while it was unchanged in the WKY. PRC was unchanged or even slightly decreased in these animals when MAP was increased by physostigmine. An AVP pressor antagonist did not attenuate the pressor and cardiac effects of physostigmine in these animals. These data indicate that an impaired baroreflex mechanism or a different mode of sympathetic neuronal activation by physostigmine through the central mechanism appears to be contributory, at least in part, to the enhanced pressor responsiveness in the SHR. The renin-angiotensin system and AVP do not appear to be involved in the enhanced pressor responsiveness to physostigmine in SHR rats.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Heart Rate; Hypertension; Male; Physostigmine; Pressoreceptors; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; Renin-Angiotensin System; Vasopressins

The present study was aimed to examine the excretory urinary Anti Diuretic Hormone (ADH) pattern in five normotensive and ten hypertensive human subjects. It was observed that Essential hypertensive subjects excreted higher urinary ADH 8.03 +/- 1.17 mU/hr as compared to 3.60 +/- 0.72 mU/hr the difference between the two groups being statistically significant (P less than 0.01). Various renal function parameters evaluated were within normal limits. The results of this study suggest the involvement of ADH in the pathophysiology of Essential hypertension.

Topics: Adult; Aged; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Vasopressins

We studied the actions of vasopressin administered microiontophoretically onto neurons of the locus ceruleus in rats with deoxycorticosterone-acetate (DOCA)-salt hypertension and in control (normotensive) rats. Rats were studied at 3 days (prehypertensive stage) and 4 to 6 weeks after DOCA-salt treatment (chronic hypertensive stage). Experiments were performed in anesthetized rats using conventional microiontophoretic and single-cell recording techniques. Three days after DOCA-salt administration, the treated rats showed no rise in arterial pressure in comparison with control rats, but 4 to 6 weeks later, the treated rats had significantly greater pressures (p less than 0.01) than controls. Vasopressin administered with currents of 10 to 90 nA for 1 minute produced a current-dependent increase in the firing rate of noradrenergic neurons in all rats. Increases in the firing rate of noradrenergic neurons in DOCA-salt-treated rats, whether in the prehypertensive or the chronic stage, were significantly greater than increases in control rats. These findings indicate that 1) vasopressin can affect neuronal activity in the locus ceruleus and 2) noradrenergic neurons in the locus ceruleus of DOCA-salt-treated rats have an increased responsiveness to the excitatory effects of vasopressin in both prehypertensive and chronic stages of hypertension.

Topics: Animals; Desoxycorticosterone; Hypertension; Iontophoresis; Locus Coeruleus; Neurons; Norepinephrine; Rats; Rats, Inbred Strains; Sodium Chloride; Vasopressins

Peptides containing the ACTH4-10 or gamma MSH3-9 sequence have varying degrees of natriuretic activity. Several of these peptides also possess pressor activity. The basis for the cardiovascular effect appears to be increased central sympathetic drive. The mechanism by which circulating gamma MSH affects central cardiovascular regulation is via an interaction with structures in the anteroventral third ventricle (AV3V) region, resulting in stimulation of the central vasopressin system. This pathway projects from the forebrain to hindbrain and spinal cord centers which regulate autonomic drive. We have extended these initial findings to other central sympathoexcitatory pressor factors, including hypertonic saline (HS) and angiotensin II (A-II). In both of these cases, the central vasopressin system mediates their autonomic effects. Since HS and A-II also work through the AV3V, the central vasopressin system may be partially responsible for the increased sympathetic drive noted in forms of hypertension which are AV3V-dependent.

Topics: Angiotensin II; Animals; Cardiovascular System; Central Nervous System; Cerebral Ventricles; Hypertension; Melanocyte-Stimulating Hormones; Natriuresis; Peptides; Rats; Saline Solution, Hypertonic; Vasopressins

Hormonal, mean arterial blood pressure, forearm blood flow and heart rate responses to graded dopamine infusion (0.5-2.0 micrograms/kg/min) were examined in 10 men with untreated essential hypertension WHO group I (147 +/- 4/100 +/- 1 mmHg, means +/- SE), and in 10 normotensive men (129 +/- 2/85 +/- 1 mmHg), all 40 years old. Another 12 normotensive men (126 +/- 3/80 +/- 2 mmHg) were given only saline infusion. Dopamine increased heart rate significantly in the hypertensive group (8 +/- 2 beats/min, p less than 0.001), but the heart rate remained unchanged in the normotensive group (1 +/- 1 beats/min, NS). Although dopamine infusion tended to decrease mean blood pressure, the changes were not significantly different from those observed in the control group. No change in forearm blood flow was observed in either group. In the groups given dopamine, prolactin levels decreased only slightly compared to the control group given saline, the decrement tending to be more pronounced in the hypertensive group. Plasma vasopressin remained unchanged in both groups during dopamine infusion. These results indicate that hypertensive patients exhibit increased sensitivity to the cardiovascular effects of dopamine.

Topics: Adult; Dopamine; Forearm; Heart Rate; Hemodynamics; Humans; Hypertension; Infusions, Intravenous; Male; Prolactin; Vasopressins

1. The role of the sympathetic nervous system and the effect of vasopressin (AVP) on the hypotensive action of nifedipine (Nf) were evaluated in conscious, unrestrained normotensive and DOCA-salt hypertensive rats. 2. The hypotensive response to Nf was much greater in DOCA rats than in the controls. 3. Solitary blockade of the sympathetic nervous system or AVP, did not alter the Nf effect in either DOCA or control rats. However, a combination clearly diminished the effect of Nf in the DOCA group, but enhanced it in the controls. The inhibition of angiotensin II (ANG II) augmented the hypotensive effect of Nf in control animals, but not in the DOCA rats. The percentage fall in blood pressure with Nf was much the same in both groups after the combined inhibition of the sympathetic nervous system and AVP. 4. The enhanced hypotensive action of Nf in DOCA rats may be dependent on the hyperactivity of the sympathetic nervous system and AVP, which facilitates calcium influx, and in the normotensive animals the depressor response to Nf may relate to blockade of the calcium influx, independent of the sympathetic nervous system, AVP and ANG II.

Topics: Analysis of Variance; Animals; Blood Pressure; Desoxycorticosterone; Heart Rate; Hypertension; Male; Nifedipine; Rats; Rats, Inbred Strains; Sympathetic Nervous System; Vasopressins

The aim of this work was to study the influence of beta-adrenoreceptor blockade on the adaptation to exercise of one of the hormonal systems (arginine vasopressin) involved in the regulation of blood volume and pressure in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) was measured in SHR and WKY rats during 11 wk of swim training. At the end of the training program we determined post-exercise values of plasma arginine-vasopressin (pAVP), osmolality (pOsm), K+ (pK+), Na+ (pNa+), hemoglobin (Hgb), and hematocrit (Hct) in SHR and WKY rats. The following groups were studied: control (C), propranolol treated (PC), swim trained (S), and propranolol-treated and swim-treated (PS). SBP was significantly reduced by swim training or propranolol, bu these beneficial effects on SBP were attenuated when propranolol and swim training were combined. pNa+ and pOsm were significantly reduced by training alone in SHR. This reduction of pNa+ and, consequently, of pOsmol without any modification of other parameters could suggest an Na+ loss. In contrast, the SHR group treated with propranolol alone showed a significant reduction in Hct, suggesting an increased plasma volume without Na+ loss. PS SHR showed a significant reduction of Hgb, Hct, proteins, pNa+, and pOsmol, probably as a consequence of the additive effects of swimming- and propranolol-induced hypervolemia with Na+ loss. The slight and nonsignificant reduction in pAVP observed with either training or propranolol treatment alone became much more pronounced and statistically significant when the 2 treatments were combined. WKY rats showed a much smaller response to exercise and beta-adrenoreceptor blockade than SHR. We conclude that the hypervolemia suggested in PS SHR could be a possible cause of attenuation of the beneficial effects of either swimming or propranolol on SBP.

Topics: Animals; Blood Pressure; Electrolytes; Hypertension; Male; Physical Exertion; Propranolol; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Swimming; Vasopressins

To investigate a possible sex difference in the development of deoxycorticosterone (DOC)-salt hypertension in rats, systolic blood pressure was measured over 6 weeks in unilaterally nephrectomized male and female rats with or without DOC-salt treatment. Throughout the treatment, systolic blood pressure was significantly lower in female than in male DOC-salt rats (at the end of the sixth week: 190 +/- 8 vs 163 +/- 7 mm Hg, p less than 0.05). The difference in blood pressure was also confirmed by the direct measurement of mean arterial pressure at the end of the experiment. The 24-hour urinary excretion of vasopressin was significantly higher in male control rats than in female control rats; however, no difference was observed between male and female DOC-salt rats, in which the urinary excretion of vasopressin was four to five times higher than in control rats. The plasma vasopressin concentration was higher in DOC-salt rats, but there were no differences between sexes. There were no differences in the metabolic clearance rate of vasopressin among the four groups of rats. This indicates that the elevated plasma vasopressin concentration in DOC-salt hypertensive rats is due to increased release of the hormone, rather than to impaired metabolism. Thus, although vasopressin plays a pivotal role in the pathogenesis of DOC-salt hypertension, the sexual dimorphism in this form of hypertension cannot be attributed to differences in the secretion, metabolism, or plasma concentration of vasopressin.

Topics: Animals; Desoxycorticosterone; Female; Hypertension; Male; Rats; Rats, Inbred Strains; Sex Characteristics; Sodium Chloride; Vasopressins

Topics: Animals; Extracellular Space; Humans; Hypertension; Ion Channels; Models, Biological; Natriuretic Agents; Renin; Sodium; Vasopressins

The role of vasopressin in human hypertension was examined in a series of studies. In patients with primary hyperaldosteronism and benign essential hypertension, circulating vasopressin was generally lower than in normotensive subjects. In contrast, plasma vasopressin was increased (p less than 0.001) in patients with malignant-phase hypertension. However, compared to infused vasopressin in normal subjects, when plasma levels of up to 120 pg/ml did not affect blood pressure, the increased levels found in malignant hypertension could not account for the hypertension. The possibility that there may be an increased pressor sensitivity to vasopressin in hypertension was examined by infusing the peptide into nine patients with essential hypertension. This showed a slight increase in sensitivity compared to normotensive subjects, but again this was insufficient to account for the discrepancy between the circulating level of vasopressin and the extent of the raised blood pressure in the hypertensive patients. The effect of chronically elevated levels of vasopressin was studied in a group of patients with the syndrome of inappropriate ADH excess as a consequence of bronchogenic carcinoma. In spite of having chronically elevated levels of vasopressin, these patients had normal blood pressures for their age and sex. Our results suggest that, although vasopressin is elevated in malignant hypertension, it does not contribute significantly to the raised blood pressure, and its increase is probably a consequence of volume shrinkage through renal salt and water loss.

Topics: Blood Pressure; Female; Humans; Hypertension; Inappropriate ADH Syndrome; Infusions, Intravenous; Male; Middle Aged; Vasopressins

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate, and skin blood flow was assessed in normotensive subjects, mild hypertensive patients, and patients with congestive heart failure, utilizing the specific antagonist of AVP at the vascular receptor level, d(CH2)5Tyr(Me)AVP (5 micrograms/kg i.v.). The renin system of the normal volunteers treated with the AVP antagonist was either intact or acutely blocked with the angiotensin converting-enzyme inhibitor captopril (25 mg p.o.). In some volunteers, the cardiovascular effect of AVP released by Finnish sauna or cigarette smoking was studied. In patients with congestive heart failure, hemodynamic measurements (pressures and cardiac output) were obtained invasively. Acute blockade of AVP vascular receptors produced no cardiovascular effect unless plasma AVP levels were markedly elevated. In our experience, abnormally high circulating AVP appears to be responsible for the decrease in skin blood flow induced by cigarette smoking and to some extent for the maintenance of vascular tone in the rare patients with particularly severe congestive heart failure.

Topics: Angiotensin II; Arginine Vasopressin; Heart Failure; Hemodynamics; Humans; Hypertension; Smoking; Steam Bath; Vasopressins

Using techniques of intracerebroventricular administration of vasopressin, microinjection of vasopressin into specific brain nuclei, electrical stimulation, and ablation of specific nuclei, we found that vasopressin, through an effect on central neural structures, increases mean arterial pressure and heart rate via an increase in sympathetic outflow and that deoxycorticosterone acetate (DOCA)-salt hypertensive rats show increased sensitivity and responsiveness to the central effects of vasopressin. Furthermore, we found that an important central target area for the cardiovascular effects of vasopressin is the pontine nucleus locus coeruleus. Ablation of the locus coeruleus markedly attenuates the cardiovascular effects of vasopressin as well as the development of DOCA-salt hypertension. Taken together, our results suggest a link between vasopressin, the locus coeruleus, and the sympathetic nervous system in normal cardiovascular regulation as well as in the pathogenesis of DOCA-salt hypertension. Our studies support the hypothesis that vasopressin modifies sympathetic drive through an action on central neural target areas, such as the locus coeruleus controlling sympathetic outflow. Our data further suggests that vasopressin may participate in the pathogenesis of DOCA-salt hypertension by inducing stimulation of the sympathetic nervous system at the region of the locus coeruleus in this model.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Electric Stimulation; Heart Rate; Homeostasis; Hypertension; Injections, Intraventricular; Locus Coeruleus; Microinjections; Rats; Rats, Inbred Strains; Vasopressins

Vasopressin secretion is stimulated by hyperosmolality, hypovolemia, or hypotension and is inhibited by hypoosmolality, hypervolemia, or hypertension. These osmotic and hemodynamic influences are mediated by neuronal afferents that originate in separate osmoreceptors or baroreceptors but ultimately converge to act on the same neurosecretory neurons. Functionally, the two control systems are integrated in such a way that osmoregulation is altered but not disrupted by hemodynamic influences. In patients with uncomplicated essential hypertension, basal as well as osmotically stimulated vasopressin is completely normal. The vasopressin response to an acute reduction in blood pressure is also normal if the values are expressed relative to the change in pressure. However, if the plasma vasopressin response is plotted as a function of absolute blood pressure, the line describing the relationship lies well to the right of normal. Thus, although it is completely intact, the baroregulatory mechanism appears to be reset to a higher level in essential hypertension. These results suggest that increased secretion of vasopressin does not contribute to the genesis or maintenance of uncomplicated, untreated essential hypertension but may antagonize the therapeutic effect of some antihypertensive drugs. If so, antagonists of V1 receptors may be useful as second-line adjunctive therapy for this condition.

Topics: Adult; Blood Pressure; Humans; Hypertension; Hypertonic Solutions; Pressoreceptors; Vasopressins; Water-Electrolyte Balance

To investigate the possible role of arginine vasopressin in maintaining high blood pressure of spontaneously hypertensive rats (SHR), the effect of two arginine vasopressin pressor antagonists on mean arterial pressure and the pressor responsiveness to exogenous arginine vasopressin were studied in conscious, freely moving SHR and in Wistar-Kyoto rats (WKY). Intravenous injections of either d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg, or dPTyr(Me)arginine vasopressin, 20 micrograms/kg, had no effect on mean arterial pressure or heart rate of normohydrated SHR, although both antagonists almost completely abolished the pressor response to exogenous arginine vasopressin. Furthermore, dPTyr(Me)arginine vasopressin was ineffective in eliciting a depressor response, even after 24 or 48 hours of water deprivation. During converting enzyme inhibition with SQ 20881, mean arterial pressure and heart rate remained unchanged following arginine vasopressin blockade in both normohydrated and fluid-restricted animals. alpha-Adrenergic receptor blockade reduced the blood pressure of normohydrated SHR, from 160 +/- 7 to 81 +/- 8 mm Hg. When dPTyr(Me)arginine vasopressin was given during alpha-adrenergic receptor blockade there was a small, transient fall in mean arterial pressure. The pressor responsiveness to exogenous arginine vasopressin was similar in hypertensive and normotensive rats. These results suggest that arginine vasopressin does not function as an important pressor hormone in conscious SHR.

Topics: Adrenergic beta-Antagonists; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Arginine Vasopressin; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Hypertension; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Vasopressins; Water Deprivation

These studies compared the importance of electrogenic Na+-K+ active (ATP driven) transport, changes in K+ conductance, and passive Ca2+-Na+ countertransport in the large relaxation that occurs in the rat caudal and basilar artery on return to K+ from K+-free solutions. Furthermore, we compared the importance of these three membrane electrical mechanisms in stroke-prone spontaneously hypertensive rats (SP-SHR) versus their normotensive Wistar-Kyoto control rats (WKY) in basilar (cerebral) and caudal arteries. We found that in both basilar and caudal arteries the hyperpolarization and relaxation that occurred on return to K+ after exposure to a 0 K+ (extracellular) solution was consistently greater in SP-SHR than in WKY. The change in membrane potential occurring on transition to 0 K+ in arteries maintained at low temperature (16 degrees C), used as an estimate of the change in K+ conductance during the K+ transition, was not different in either basilar or caudal arteries between SP-SHR and WKY. Thus the hyperpolarization on return to K+ at body temperature would depend primarily on the level of activity of the membrane ATPase, referred to as the Na+ pump. We also sought to compare the passive (but electrogenic) Ca2+-Na+ countertransport mechanism between strains for both arteries, but we were unable to detect any evidence of the predicted hyperpolarization-contraction on transition from 145 to 10 mM extracellular Na+. Furthermore, the return to extracellular Na+ solution failed to show the depolarization-relaxation predicted by the Ca2+-Na+ countertransport mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphatases; Animals; Biological Transport, Active; Diastole; Electric Conductivity; Hypertension; Membrane Potentials; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Myocardium; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Vasopressins

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Extracellular Space; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Natriuresis; Natriuretic Agents; Prostaglandins; Rabbits; Rats; Renal Circulation; Renin; Sodium; Sodium-Potassium-Exchanging ATPase; Vasopressins

The effects of continuous intravenous infusion of naloxone or vehicle on the blood pressure and vasopressin responses to step-wise hemorrhage were examined in conscious, age-matched spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Step-wise hemorrhage progressively lowered blood pressure and increased plasma vasopressin levels in both SHR and WKY. The WKY were relatively resistant to the hypotensive effect of hemorrhage. No significant differences were noted in blood pressure responses between naloxone-treated and vehicle-treated SHR while naloxone treatment attenuated hypotension only slightly in WKY. Plasma vasopressin levels were also elevated by naloxone treatment in SHR following a nonhypotensive hemorrhage equivalent to 0.5% of body weight. However, no differences were observed between plasma vasopressin levels in naloxone-treated and vehicle-treated SHR at greater degrees of hemorrhage. In addition, plasma vasopressin levels were similar at all times in hemorrhaged WKY, regardless of treatment. Plasma vasopressin levels were increased by naloxone in both time-control SHR and WKY. The data demonstrate that naloxone-sensitive systems exert only minimal effects on the immediate cardiovascular responses to hypovolemia in normotensive rats and no measurable effects in SHR. It does appear that naloxone-sensitive mechanisms contribute a small, but significant, tonic inhibitory influence over vasopressin secretion in both normotensive and hypertensive rats under basal conditions and in SHR in response to a small reduction in blood volume.

Topics: Animals; Blood; Blood Pressure; Heart Rate; Hemorrhage; Hypertension; Male; Naloxone; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Opioid; Vasopressins

We characterized altered adenosine 3',5'-cyclic monophosphate (cAMP) regulation in deoxycorticosterone acetate (DOCA)-Na hypertensive rats using endogenous cAMP accumulation in the intact cell system of microdissected renal tubule fragments. Increased cAMP accumulation in response to vasopressin (VP) in cortical collecting tubules (CCT) began on day 5 (67%) after exposure to DOCA-Na and increased by 320% on day 42. Increased blood pressure began after day 7 and polyuria after day 17. The increased response to VP was DOCA dependent and appears to be exaggerated by dietary NaCl. Anatomic and hormone specificity studies were done on days 21-30. These included cAMP responses to prostaglandin E2, parathyroid hormone, thyrocalcitonin, VP, and isoproterenol in the CCT. The cAMP response to VP was measured in the glomerulus, proximal convoluted tubule, thin descending limb of Henle, medullary thick ascending limb of Henle, cortical thick ascending limb of Henle, medullary collecting tubule, and CCT. The supersensitivity occurred only to VP and only in the CCT. Thus this alteration in the VP response is anatomic and hormone specific and does not appear to be an acute effect of DOCA, since it was not present on day 1 and on day 3 of DOCA exposure. DOCA-Na hypertension is VP dependent. A specific exaggerated cAMP response to this hormone in the CCT would be expected to cause increased sodium retention. Whether increased sodium retention at this site contributes to hypertension in the DOCA-Na rat is unknown.

Topics: Animals; Blood Pressure; Cyclic AMP; Desoxycorticosterone; Hypertension; In Vitro Techniques; Kidney; Kidney Tubules; Kinetics; Male; Rats; Rats, Inbred Strains; Vasopressins

Electrolytic lesions of the A1 noradrenaline cells in the caudal ventrolateral medulla cause transient hypertension and bradycardia in the conscious rat, as previously described in the rabbit. The lesions produced 100-fold increases in plasma arginine vasopressin, 40-fold increases in plasma adrenaline and fourfold increases in plasma noradrenaline levels. Absence of circulating vasopressin [homozygous diabetes insipidus rats (DI)] or circulating adrenaline (adrenalectomized rats) did not affect A1 hypertension, but sympathectomy with systemic 6-hydroxydopamine (6-OHDA) significantly attenuated A1 hypertension. A factorial experiment was performed to assess the relative contributions of these three peripheral effector mechanisms in a quantitative manner, with combined deficiencies of any two or of all three of these effector systems. Results suggest A1 hypertension in the rat to be primarily mediated through increased sympatho-adrenal activity. The largest component of hypertension (66%) results from increased sympathetic vasoconstrictor nerve activity, and a smaller part (34%) reflects the action of circulating adrenaline. Increases in vasopressin levels do not contribute to A1 hypertension, although vasopressin makes a major contribution to A1 lesion bradycardia.

Topics: Adrenalectomy; Analysis of Variance; Animals; Blood Pressure; Brain; Epinephrine; Heart Rate; Hydroxydopamines; Hypertension; Male; Medulla Oblongata; Oxidopamine; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Inbred WKY; Sympathetic Nervous System; Vasopressins

Histological analysis of the catecholaminergic innervation of vasopressin neurons in the supraoptic nucleus (SON) was performed using catecholamine histofluorescence and immunocytochemistry of vasopressin specific neurophysin (VP-NP) in order to determine if spontaneously hypertensive rats (SHR) demonstrate alterations in the relationship between these two types of chemically defined neurons. Chronically hypertensive SHRs showed an increased density of catecholamine fluorescence particularly in the dorsal part of the SON in comparison to age-matched, normotensive, Wistar-Kyoto (WKY) rats, but not in comparison to age-matched Wistar rats. In addition, there was an increase in the area of distribution of VP-NP immunopositive neurons such that they extended into the dorsal portion of the nucleus in the SHR compared to the WKY. Comparator bridge analysis of immunocytochemical staining and catecholamine histofluorescence revealed a precise overlap of the two patterns in SHR. Thus, the more extensive distribution of catecholamine fluorescence in the dorsal SON in the SHR compared to WKY paralleled the more extensive distribution of VP neurons in this region. Quantitative analysis of the relative percentage of SON neurons which were VP-NP positive indicated that the increased representation of VP-NP positive neurons in the dorsal portion of the nucleus reflected a greater distribution of the VP-NP cell population throughout the SON rather than an increase in the number of VP-NP neurons in the SHR. In young SHRs (5 weeks old) the catecholamine fluorescence pattern in the SON was considerably smaller than that observed in older SHRs. This low density pattern, however, was comparable to that observed in young WKYs. Thus, the catecholamine fluorescence in the SON apparently increases in the SHR in parallel with the development of the hypertension. This observation and the finding of comparable catecholamine fluorescence in Wistars and SHRs suggest that the altered catecholamine innervation of VP neurons observed in chronically hypertensive SHRs is not causal to the hypertension but may reflect a response to the elevated blood pressure. A marked increase in the catecholamine innervation of cerebral arteries was also noted.

Topics: Age Factors; Animals; Blood Pressure; Hypertension; Immunoenzyme Techniques; Male; Microscopy, Fluorescence; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Species Specificity; Supraoptic Nucleus; Vasopressins

Different levels of water-salt metabolism control were studied in patients with stable essential hypertension (SEH). The sample was found to be highly heterogeneous in terms of the magnitude of the body's water-filled spaces in relation to plasma renin activity (PRA) and the cooking salt gustatory sensitivity threshold, examined in the presence of various salt diets and diuretic treatments. Three patterns of response to salt loads were identified in SEH patients with respect to sodium and water elimination by the kidneys: the first was identical to that of normal subjects, while the second one featured increased, and the third one, decreased, diuresis and natriuresis. Prostaglandin E2 and kallikrein were shown to be involved in the formation of the second- and third-type renal response to excessive salt. Differential treatment of EH patients with diuretics alone or, where necessary, in combinations with small-dose beta-blockers or vasodilators provides effective BP control for some 1.5 to 2 years in 65% of patients.

Topics: Adult; Body Fluid Compartments; Body Water; Dinoprost; Dinoprostone; Diuretics; Furosemide; Humans; Hypertension; Kallikreins; Male; Middle Aged; Plasma Volume; Prostaglandins E; Prostaglandins F; Renin; Sodium Chloride; Vasopressins; Water-Electrolyte Balance

Abnormalities in the vasopressin (VP) and renin-angiotensin systems have been described in spontaneously hypertensive rats (SHR). Responsiveness of these systems to a decrease in plasma volume was examined in the SHR at 6, 8, and 18 wk of age and compared with responses in age-matched normotensive Wistar and Wistar Kyoto rats (WKY). Trunk blood was collected 3 h after administration of 2 ml/100 g body wt of 0.9% saline, 15 or 30% polyethylene glycol (PEG), and in one group of conscious 8- and 18-wk-old rats, mean arterial pressure was monitored following PEG administration. Hematocrit and serum VP increased significantly in both strains at all ages following PEG. At 6 and 8 wk of age, the VP response to the PEG injection was significantly greater in SHR compared with WKY (P less than 0.005), but at 18 wk the response was comparable in the two strains. Serum renin activity (SRA) also increased in both strains receiving PEG at 6 and 8 wk of age, but the response was suppressed in the SHR relative to the WKY (P less than 0.001). At 18 wk of age, SRA increased in WKY, but the response was totally suppressed in SHR. Renal renin content in a separate group of rats was reduced in 19-wk-old SHR compared with WKY (P less than 0.001) but was not different in 5- and 8-wk-old rats. Thus there appears to be a hyperresponsiveness in the VP system in young SHRs that is not present in the renin-angiotensin system. The divergence in the responsiveness of the renin and VP systems and the attenuation of responsiveness in the VP system in 18-wk SHRs indicate a differential effect of the hypertensive process on the VP and renin systems in the SHR.

Topics: Aging; Analysis of Variance; Animals; Blood Pressure; Blood Volume; Hematocrit; Hypertension; Hypothalamus; Kidney; Male; Pituitary Gland, Posterior; Polyethylene Glycols; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renin; Vasopressins

The antihypertensive effect of blockade of the brain renin-angiotensin system (brain RAS) was investigated in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Continuous intracerebroventricular (ICV) administration of SQ14225 (SQ; 1.25 micrograms X 0.5 microliter-1 X h-1) for 7 days attenuated the increase in blood pressure (99 +/- 5 vs. 116 +/- 4 mmHg on the 7th day) and also reduced the elevation of blood pressure (157 +/- 7 vs. 138 +/- 6 mmHg) in these hypertensive rats. Attenuation of increasing blood pressure in the developing phase following ICV SQ treatment was accompanied by decrease of fluid intake and prevention of elevation of the plasma vasopressin. In the established phase, in addition to reduction of the plasma vasopressin and decrease of fluid intake, restoration of the impaired baroreceptor reflexes was brought about by ICV SQ treatment. These results indicate that the brain RAS strongly influences the regulation of blood pressure in DOCA-salt hypertensive rats and that its mechanism of action is closely related to changes in sodium excretion, vasopressin, and the baroreceptor reflexes.

Topics: Aldosterone; Angiotensin I; Angiotensin II; Animals; Blood Pressure; Brain; Captopril; Desoxycorticosterone; Diuresis; Drinking; Hematocrit; Hypertension; Injections, Intravenous; Injections, Intraventricular; Male; Pressoreceptors; Rats; Rats, Inbred WKY; Reflex; Renin; Renin-Angiotensin System; Sodium; Sodium Chloride; Vasopressins

Seventeen 50-year-old hypertensive men (157 +/- 4/110 +/- 2 mmHg, mean +/- SE) were given low sodium diet for one week, which was supplemented with potassium the following week. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:5 and 1:12, respectively, during dietary intervention. Arterial plasma vasopressin decreased by 3.4 +/- 1.7 ng/l (0.05 less than p less than 0.10) and urinary excretion of vasopressin was reduced by nearly 50% (p less than 0.001) during sodium depletion, while plasma noradrenaline increased by 38% (p less than 0.001) and plasma dopamine showed an increase by 58% (p less than 0.001). Plasma renin concentration increased four-fold during sodium depletion (p less than 0.001). With combined salt depletion and potassium supplementation, arterial plasma vasopressin decreased by 9.5 +/- 4.0 ng/l (p less than 0.05) compared to control. Urinary excretion of vasopressin together with plasma noradrenaline and dopamine were unchanged during the second week. The reduction of blood pressure was most marked during the first week (143 +/- 3/103 +/- 2 mmHg, p less than 0.05), but continued to fall also during the second week. Thus, during sodium restriction in middle-aged hypertensive men, blood pressure reduction occurs concomitantly with inhibited vasopressin release, despite enhanced renin and catecholamine release. Potassium supplementation during sodium restriction induces only minor changes in these variables.

Topics: Blood Pressure; Diet, Sodium-Restricted; Dopamine; Epinephrine; Humans; Hypertension; Kidney; Male; Middle Aged; Potassium; Renin; Sodium; Vasopressins

In 10 patients undergoing routine coronary artery surgery, plasma renin activity and vasopressin concentration were measured at intervals before the induction of anaesthesia, and for 6 h after bypass. In three patients plasma renin activity was increased, but the increases followed no particular pattern. Vasopressin concentrations increased in all 10 patients, but the changes were not significantly correlated with the postoperative arterial hypertension that was seen in seven of the patients.

Topics: Adult; Aged; Coronary Artery Bypass; Humans; Hypertension; Intraoperative Period; Middle Aged; Postoperative Complications; Postoperative Period; Renin; Vasopressins

The main purpose of this study was to evaluate changes in plasma arginine vasopressin (AVP) associated with arterial baroreceptor deafferentation. Food and water intake of sham-operated (SO) rats was matched to that of sinoaortic denervated (SAD) rats, and blood samples were collected from groups of SAD and SO rats 15 min, 1-4 h, 24 h and 4-7 days after operation. Plasma AVP was 2-4 times higher in SAD than SO rats at each of the times studied during the 1st week (p less than 0.001); at those times no significant differences in hematocrit, plasma sodium or osmolality were found. Three weeks after surgery, plasma AVP was similar in both groups of rats. Mean arterial pressure, measured in additional groups of rats, was approximately 35 mm Hg higher in SAD than SO rats for the first 4 postsurgical hours, remaining about 20 mm Hg higher at the later times. Administration of an AVP pressor antagonist to SAD rats caused a small (8-11%), statistically significant reduction in the elevated pressure of SAD rats during the first 4 postsurgical days. Thus, AVP contributes modestly to the elevation of arterial pressure caused mainly by neurogenic mechanisms in SAD rats during the early postoperative period. Ingestive behavior was monitored in additional SO and SAD rats. SAD rats had significantly reduced food and water intake for 5 days after surgery, however, by day 6 intake was comparable to that of SO rats. Preoperative body weight was not regained until 2 weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Denervation; Eating; Hypertension; Male; Pressoreceptors; Rats; Rats, Inbred Strains; Sinus of Valsalva; Time Factors; Vasopressins

Pressor responses and heart rate responses to intravenous injections (3.5-50.0 pmol/kg) of arginine vasopressin (AVP) were recorded in saline- and clonidine-treated spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Clonidine (20 micrograms/kg, i.v.) caused a marked fall of arterial pressure in SHR but not in WKY rats so that, 20 min after the injection of the alpha 2-adrenoceptor agonist, arterial pressure was similar in the two strains of rats. The curve expressing the relationship between the dose of AVP and the increase of arterial pressure for saline-treated SHR was positioned to the left of that for saline-treated WKY rats. This enhanced pressor responsiveness of SHR to AVP may have been related to impaired reflex activity since heart rate fell much less in SHR than in WKY rats for a given elevation in pressure. Pressure responses to AVP were augmented by clonidine in both SHR and WKY rats so that, similar to saline-treated rats, pressor responsiveness to the peptide was still greater in SHR. Heart rate responses to AVP were not altered significantly by clonidine. The results indicate that clonidine fails to enhance reflex activity and reduce pressor responsiveness of SHR to AVP. The increased pressor responsiveness of both SHR and WKY rats to AVP following clonidine was an unexpected finding and may be related to a peripheral interaction between alpha-adrenergic agonists and AVP.

Topics: Animals; Blood Pressure; Clonidine; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Vasopressins

Enkephalins are found in the posterior pituitary, can alter vasopressin secretion, and have greater pressor effects in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats. Measurement of the plasma methionine-enkephalin concentration (PMet-Enk) has provided equivocal results in humans and has not been reported in rats. We have developed a highly specific and sensitive Met-Enk radioimmunoassay and determined that Met-Enk circulates in rats but that PMet-Enk is no different between SHR and WKY rats (7.6 +/- 0.8 and 9.2 +/- 0.8 pg/ml, respectively). Water deprivation for 48 h increased the plasma vasopressin concentration (PADH) and 24-h urinary vasopressin excretion (UADHV) in SHR and WKY rats, but PMet-Enk was not altered. There were no differences in PADH and UADHV between SHR and WKY rats in either the euhydrated or dehydrated state. These results suggest that it is unlikely that circulating Met-Enk contributes importantly to the maintenance of hypertension in SHR. There was also no evidence for a greater secretion of vasopressin in SHR than in WKY rats, in contrast to previous reports.

Topics: Animals; Blood Pressure; Body Weight; Dehydration; Diuresis; Enkephalin, Methionine; Heart Rate; Hypertension; Male; Osmolar Concentration; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Vasopressins

To determine whether there is a change in the sensitivity of the osmotic control of vasopressin release in deoxycorticosterone (DOC)-salt hypertension, experiments were performed in unilaterally nephrectomized rats that were either normotensive or were made hypertensive with DOC and given 1% saline to drink. After 3 weeks of treatment, 2.5 mol/l NaCl was infused i.v. into conscious normotensive and hypertensive rats. Increases in both plasma osmolality and plasma vasopressin concentration were similar throughout the course of this infusion in the two groups of rats. Hypertonic saline infusion increased the mean arterial blood pressure in the two groups of rats, but this increase was partially attenuated by the i.v. injection of a vasopressin pressor antagonist. In conclusion, vasopressin release in response to osmotic stimulation was similar in normotensive and hypertensive rats. The pressor response to hypertonic saline in both groups of rats could be partially attributed to the increased plasma vasopressin concentration.

Topics: Animals; Blood Pressure; Desoxycorticosterone; Hypertension; Male; Osmolar Concentration; Osmotic Pressure; Potassium; Rats; Rats, Inbred Strains; Sodium; Sodium Chloride; Vasopressins

The roles of vasopressin, the sympathoadrenal system, and the renin-angiotensin system in the production of hypertension after bilateral destruction of the nucleus tractus solitarius (NTS) were examined in chloralose-anesthetized rats. Since the activity of the renin-angiotensin system is high in anesthetized rats, additional studies were performed in unanesthetized, freely moving rats to evaluate the role of the renin-angiotensin system in hypertension caused by NTS lesions. Hypertension produced by bilateral electrolytic NTS lesions in rats was accompanied by elevated plasma levels of vasopressin (approximately 7-fold), norepinephrine (greater than 10-fold), and epinephrine (greater than 10-fold), but not of plasma renin activity. These results suggest that this form of hypertension is due to increased sympathoadrenal activity and increased vasopressin release into plasma and that the renin-angiotensin system is not involved. In rats with NTS lesions, blockade of vasopressin or the sympathoadrenal system, but not the renin-angiotensin system, elicited an acute decrease in arterial pressure. However, blockade of either vasopressin or the autonomic nervous system before production of the lesions had no effect on the resulting hypertension, indicating that in the absence of either one of these systems bilateral NTS lesions still result in severe hypertension. Although the renin-angiotensin system does not normally contribute to this hypertension, it does appear to contribute to the elevation in blood pressure once the actions of vasopressin have been blocked. In rats pretreated with a vasopressin antagonist, plasma renin activity increased following NTS lesions and the angiotensin converting enzyme inhibitor captopril decreased blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Medulla; Animals; Hypertension; Male; Medulla Oblongata; Pressoreceptors; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Sympathetic Nervous System; Vasopressins

The purpose of this study was to examine, using pentobarbital-anesthetized rats, whether vasopressin contributes to hypertension caused by denervation of baroreceptors, in comparison to the contribution of vasopressin to hypertension caused by nucleus tractus solitarius (NTS) lesions. Bilateral baroreceptor denervation caused acute hypertension which was inhibited by intravenous injection of an antagonist of the vasoconstrictor action of vasopressin. Lesions of the NTS also produced an increased in blood pressure which was reduced by the vasopressin antagonist. The magnitude of the antagonist-induced hypotension was significantly greater in NTS hypertension than that in baroreceptor denervation hypertension. It is concluded, that in rats, vasopressin contributes to the neurogenic hypertension caused by baroreceptor denervation and NTS lesions. Thus, it appears that interruption of baroreceptor afferents at the NTS level is responsible for the vasopressin-mediated hypertension caused by NTS lesions but that it is not the only factor involved.

Topics: Animals; Blood Pressure; Denervation; Hypertension; Male; Medulla Oblongata; Pressoreceptors; Rats; Rats, Inbred Strains; Vasopressins

Monopolar electrical stimulation of the intermediate portion of the solitary nucleus in spontaneously hypertensive rats (SHRs) with cervical cordotomy and vagotomy resulted in a 1.68 times greater increase in plasma vasopressin concentration than in Wistar rats. The result implies that such an enhanced function of the central neural mechanism to release vasopressin in SHR backs up the functionally aberrant cardiovascular receptors.

Topics: Animals; Cardiovascular System; Electric Stimulation; Hypertension; Male; Medulla Oblongata; Pressoreceptors; Rats; Rats, Inbred SHR; Vasopressins

Plasma oxytocin-associated neurophysin concentration [( OT-RNP]) was used to evaluate the responsiveness of oxytocinergic neurons to an acute salt load in Long-Evans (LE) rats and Brattleboro homozygous (DI) rats. This responsiveness was compared with that of vasopressinergic neurons in LE rats as indexed by plasma vasopressin-associated neurophysin concentration [( VP-RNP]). Acute salt loading was induced by infusing 18% saline for 60 min into conscious, trained, chronically catheterized animals and plasma osmolality (Posm) and mean arterial pressure (MAP) were monitored. An increase in Posm was associated with a rise in [OT-RNP] and the relationship between delta [OT-RNP] and delta Posm was similar for both LE and DI rats over the first 40 min of infusion (21.6 and 19.7 fmol ml-1 mosm-1 kg-1, respectively). Although Posm continued to rise between 40 and 60 min infusion, [OT-RNP] actually fell slightly during this period in LE rats to a final elevation of 682 +/- 40 fmol/ml above initial values whereas [OT-RNP] in DI rats continued to rise to a final elevation of 1,927 +/- 288 fmol/ml above initial values at 60 min of infusion. The differences between these elevations at 60 min for LE and DI rats were highly significant (p less than 0.001). For LE rats, the increase of [OT-RNP] with Posm for the first 40 min of infusion was much greater than the increase in [VP-RNP] with the slope between delta [VP-RNP] and delta Posm being only 8.3 compared to 21.6 fmol ml-1 mosm-1 kg-1 in the case of delta [OT-RNP].(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Hypertension; Male; Neurons; Neurophysins; Osmolar Concentration; Oxytocin; Rats; Rats, Brattleboro; Saline Solution, Hypertonic; Sodium Chloride; Vasopressins

We have reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius of urethan-anesthetized normotensive rats produces an increase in mean arterial pressure (MAP) over the dose range 50-500 pmol. The effect in spontaneously hypertensive rats (SHR) is now reported. Over the range 100-500 pmol SHR exhibit increases in MAP and heart rate greater than Wistar-Kyoto or Sprague-Dawley rats. SHR did not exhibit exaggerated responses to intravenous phenylephrine, suggesting a central site of increased responsiveness to ANG II. We also found depressor effects in Sprague-Dawley at lower doses (0.1 and 1 pmol). The decreases in MAP were extremely variable and not dose related. A selected dose of additional neuropeptides identified in the NTS was tested. Somatostatin, bradykinin, and vasoactive intestinal peptide (0.5 nmol) were without cardiovascular effects. Oxytocin and vasopressin, however, produced significant increases in MAP. Substance P produced a very small but significant increase in heart rate and MAP. Interaction between the vasopressin and ANG II pressor effects was studied, and each proved to be independent.

Topics: Angiotensin II; Angiotensins; Animals; Blood Pressure; Brain Stem; Heart Rate; Hypertension; Male; Microinjections; Nerve Tissue Proteins; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Vasopressin; Species Specificity; Vasopressins

The effect of the chronic administration of captopril on plasma levels of vasopressin (PVP) were studied in 14 patients with moderate essential hypertension and 10 normal volunteers. All patients were studied after 10 days without drugs and under a constant diet (120 mmol sodium and 80 mmol potassium/day). Plasma levels of renin activity (PRA), aldosterone (PA) and PVP were assayed before and after captopril treatment (50-100 mg/day for 1 month). In addition to the well-known effect of captopril treatment on PRA and PA, a statistically significant reduction of PVP was observed. This finding suggests that the renin-angiotensin-aldosterone system influences vasopressin release, and its inhibitors may contribute to the absence of water retention during captopril treatment compared with the effect of other vasodilatory drugs.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Female; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System; Vasopressins

Topics: Adult; Female; Genitalia, Female; Humans; Hypertension; Middle Aged; Ornipressin; Vasopressins

Topics: Angiotensin II; Animals; Hypertension; Kallikreins; Male; Norepinephrine; Prostaglandins E; Rats; Rats, Inbred Strains; Vasopressins

Topics: Animals; Humans; Hypertension; Kallikreins; Kinins; Potassium; Prostaglandins; Rats; Renin-Angiotensin System; Sodium; Vasopressins

The purpose of the study was to clarify the mechanism(s) of glucocorticoid-induced hypertension. Hypertension was induced in rats by single i.m. injection of methylprednisolone (MP) 20 mg/kg. In normal Wistar rats, systolic blood pressure (SBP) increased by 30 mmHg from days 2 to 10 after MP. Urinary sodium excretion increased transiently and sodium balance was negative. Plasma volume (PV; ml/100 g body weight) increased on day 5, but was unchanged on day 2 after MP, at a time when SBP had already increased. In rats with chronic renal failure (CRF) and low sodium intake, SBP increased more than in control rats (48 versus 22 mmHg on day 10). Hypertension was not accompanied by a significant drop in urinary excretion of prostaglandin E2 (PGE2; measured by radio-immunoassay). In normal MP-injected rats, PGE2 excretion decreased slightly and then increased; in CRF rats, basal PGE2 excretion was too low to evaluate the effect of MP. In homozygous Brattleboro rats lacking antidiuretic hormone (ADH), MP increased SBP by 28 mmHg (day 10). Similar changes were obtained in heterozygous Brattleboro rats. The changes in PV were identical to those found in Wistar rats. We conclude that increase in PV, change in PGE2 and vasopressin do not play a key role in MP hypertension. Direct effect of glucocorticoid on vascular receptors is likely to be involved in this model.

Topics: Animals; Blood Volume; Diet, Sodium-Restricted; Dinoprostone; Disease Models, Animal; Female; Hypertension; Kidney; Male; Methylprednisolone; Nephrectomy; Prostaglandins E; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins

Results obtained in the control of oesophageal varix rupture haemorrhage by intravenous vasopressin perfusion or selective intraarterial administration are reported. This comparative study shows intravenous administration to be the best method since it produces the same therapeutic effects with fewer undesirable side-effects than when administered arterially. In view of the high level of complications caused by selective arterial catheters, this administration method would only appear justified in cases where selective arterial catheterisation is to be carried out in any case.

Topics: Adult; Aged; Arrhythmias, Cardiac; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension; Injections, Intra-Arterial; Injections, Intravenous; Male; Middle Aged; Vasopressins

Oral administration of the angiotensin I-converting enzyme inhibitor captopril produced a substantial reduction of blood pressure in DOCA-salt hypertensive rats. After oral administration of captopril (30 mg/kg), mean blood pressure decreased from 172 +/- 11 to 148 +/- 9 mmHg (P less than 0.01) in one hour and its antihypertensive effects lasted for the next seven hours. Plasma vasopressin levels showed a marked elevation in DOCA-salt hypertensive rats compared with control values (22 +/- 5 versus 5 +/- 3 pg/ml). This increase in vasopressin was significantly reduced by captopril from 25 +/- 5 to 8 +/- 6 pg/ml. In addition, whole body vascular reactivity to norepinephrine was examined. Responsiveness was at first attenuated but returned to control value in spite of reduction of both plasma vasopressin and blood pressure. Thus, captopril reduces blood pressure in DOCA-salt hypertensive rats and the fall in blood pressure is accompanied by reduction of plasma vasopressin and attenuation of vascular reactivity.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Captopril; Desoxycorticosterone; Hypertension; Male; Norepinephrine; Proline; Rats; Rats, Inbred Strains; Sodium Chloride; Vasopressins

Topics: Adult; Aldosterone; Blood Pressure; Humans; Hypertension; Immersion; Plasma Volume; Renin; Vasopressins

Topics: Adult; Aldosterone; Female; Humans; Hypertension; Male; Renin; Renin-Angiotensin System; Vasopressins

Topics: Adult; Alcohol Drinking; Alcoholism; Aldosterone; Blood Pressure; Double-Blind Method; Ethanol; Humans; Hydrocortisone; Hypertension; Renin; Time Factors; Vasopressins

In adult and old rabbits, the bioelectrical activity of supraotic, ventromedial and mamillary hypothalamic nuclei was studied after chronic (30 days) administration of vasopressin (0.2 U/kg of body weight). The hormone altered considerably the bioelectrical activity, these changes being uneven in various hypothalamic areas. Quantitative and qualitative differences of the changes were found in animals of different age. These changes of the hypothalamic bioelectrical activity seem to play an important role in the alterations of hemodynamic indices observed during chronic vasopressin administration.

Topics: Age Factors; Animals; Chinchilla; Female; Hemodynamics; Hypertension; Hypothalamus; Male; Mammillary Bodies; Supraoptic Nucleus; Vasopressins; Ventromedial Hypothalamic Nucleus

Pressor responses and heart rate responses were recorded in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto (WKY) rats during intravenous infusions of arginine vasopressin and phenylephrine under two experimental situations, first when cardiovascular reflexes were impaired by pretreatment with a ganglionic blocking agent (pentolinium) and second, when reflexes remained intact. In rats with ganglia blocked, pressor responses of SHR to vasopressin or to phenylephrine were similar to those of WKY rats. In rats with intact reflexes, pressor responses of SHR to phenylephrine were also similar to those of WKY rats but, in contrast, pressor responses of SHR to vasopressin were enhanced. Heart rate fell much more for any given elevation of blood pressure in WKY rats than in SHR during infusions of vasopressin and phenylephrine, and the bradycardia associated with these pressor agents was largely abolished by pentolinium. The results are consistent with the hypothesis that baroreflexes buffer the pressor activity of vasopressin in the normotensive WKY rat and that an impairment of baroreflex activity in SHR contributes to the enhanced pressor activity of vasopressin in these rats.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Ganglia; Heart Rate; Hypertension; Nerve Block; Pentolinium Tartrate; Phenylephrine; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Reflex; Vasopressins

The hypothalamo-neurohypophysial system is altered in the spontaneously hypertensive rat (SHR). We hypothesized that an aberrant regulation of vasopressin (VP) and oxytocin (OT) release by endogenous opioid peptides alters this neuroendocrine system in the SHR. Concentrations of the neurohypophysial hormones in plasma and the pituitary were measured in 17-week-old SHRs and two strains of normotensive controls. Wistar Kyoto (WKY) and Sprague-Dawley rats. Animals were decapitated 20 min after s.c. injection of saline (1 ml/kg) or naloxone hydrochloride (1 or 10 mg/kg). In addition, neurohypophysial hormones excreted during the day (08.00-17.30 h) and night (17.30-08.00 h) were determined in urine from 16-week-old animals kept in metabolic cages for 5 days. VP at extrahypothalamic sites was also measured as [VP] in acid extracts of the subfornical organ area, hippocampal commissure-fornix and choroid plexus. Hormones were quantified by radioimmunoassay. The pituitary content, plasma concentration, and urinary excretion of OT were reduced (P less than 0.05) in SHRs, whereas VP content was increased (P less than 0.05) in the pituitary and plasma, but unchanged in urine, of hypertensive animals. In extrahypothalamic tissues, [VP] in the hippocampal commissure-fornix was increased in the SHR. Naloxone elevated (P less than 0.05) the plasma concentration of OT in WKY animals and VP in SHRs. Neither [VP] nor [OT] in plasma was changed by naloxone in Sprague-Dawley rats. Pituitary stores of the neurohypophysial hormones were not altered by naloxone in either hypertensive or normotensive rats. In conclusion, endogenous opioid peptides tonically inhibit OT release in WKY rats, whereas VP release is decreased by opioid peptides in SHRs, 16-17 weeks of age. The neuromodulatory role of opioid peptides in the release of neurohypophysial hormones appears to be altered in the SHR such that VP release is suppressed and OT release is augmented.

Topics: Animals; Endorphins; Hypertension; Hypothalamo-Hypophyseal System; Male; Naloxone; Oxytocin; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Vasopressins; Water-Electrolyte Balance

Central catecholaminergic activity was studied by measurement of norepinephrine (NE), epinephrine (EPI), their metabolites: total 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylglycol in brain nuclei in response to bilateral dorsomedullary knife-cut (DMK-cut) in rats. In saline-pretreated conscious rats DMK-cut caused a marked hypertension, tachycardia and increases in plasma NE, EPI and vasopressin. Chlorisondamine (CHL) prevented the rise in plasma catecholamines and the tachycardia but failed to prevent the hypertension and the increment in plasma vasopressin. DMK-cut decreased NE and EPI in the nucleus tractus solitari (NTS) and A2 area; there were no catecholamine changes in A1 area or the periventricular nucleus but an increase in the paraventricular nucleus (PVN), the latter effect reversed by CHL. CHL alone or combined with DMK-cut had no effect on catecholamine concentrations in NTS-A2 area but lowered MHPG content. It is suggested that DMK-cut decreases the activity of the catecholaminergic system originating in A1 and terminating in PVN, where it causes catecholamine accumulation and may be involved in vasopressin release and thereby contribute to hypertension. In NTS-A2 area, however, the DMK-cut appears to increase catecholaminergic activity since catecholamines are depleted. Central effects of DMK-cut differ from those of ganglionic blockade-induced inhibition of the baroflex presumably due to sectioning of other pathways in addition to the primary baroreceptor input.

Topics: Animals; Brain Chemistry; Catecholamines; Female; Heart Rate; Hypertension; Medulla Oblongata; Methoxyhydroxyphenylglycol; Norepinephrine; Pressoreceptors; Rats; Vasopressins

The effect of clonidine on vasopressin release was studied in chloralose anesthetized rats which were made hypertensive by bilateral electrolytic lesions of the nucleus tractus solitarii (NTS). NTS lesions elevated arterial pressure and plasma vasopressin levels, and both of these variable were returned toward baseline values by intravenous injection of clonidine (30 micrograms/kg). Furthermore, the ability of a vasopressin antagonist to lower arterial pressure in NTS hypertensive rats was markedly attenuated by clonidine treatment. In contrast, autonomic blockade (chlorisondamine, 2.5 mg/kg) in NTS lesioned rats did not reduce plasma vasopressin levels or the effect of the vasopressin antagonist on blood pressure. These data demonstrate that part of the antihypertensive effect of clonidine in NTS hypertensive rats is due to inhibition of vasopressin release into the circulation.

Topics: Animals; Blood Pressure; Catecholamines; Chlorisondamine; Clonidine; Electric Stimulation; Heart Rate; Hypertension; Male; Medulla Oblongata; Radioimmunoassay; Rats; Rats, Inbred Strains; Vasopressins

Baseline plasma vasopressin concentrations were measured in 10 healthy women during a normal menstrual cycle, 97 normal women during pregnancy and 43 pregnant women hospitalized during the third trimester because of pregnancy-induced hypertension (PIH). Plasma vasopressin levels were also measured in 44 normal pregnant women in early labor and in 30 parturients at delivery. The random plasma vasopressin concentrations did not vary significantly between the nonpregnant women during the follicular phase (2.3 +/- 0.2 microU/ml) and luteal phase (2.2 +/- 0.3 microU/ml) or during the third trimester in normal pregnant women (2.0 +/- 0.2 microU/ml) or those with PIH (2.0 +/- 0.1 microU/ml). There was a significant reduction (p less than 0.01) in plasma vasopressin levels in the pregnant women during the first trimester (1.5 +/- 0.1 microU/ml) and second trimester (1.5 +/- 0.1 microU/ml) as compared to levels in nonpregnant and pregnant women in the third trimester. The mean plasma vasopressin levels in the pregnant women complaining of nausea were similar to those in the pregnant women without nausea. Plasma vasopressin levels in women during labor did not increase significantly over third-trimester-pregnancy concentrations during the first stage of labor (1.9 +/- 0.1 microU/ml) or at delivery (1.8 +/- 0.1 microU/ml). These cross-sectional measurements of maternal plasma vasopressin levels do not support a role for vasopressin in the development of PIH or in the initiation or maintenance of labor.

Topics: Arginine Vasopressin; Female; Follicular Phase; Humans; Hyperemesis Gravidarum; Hypertension; Labor, Obstetric; Luteal Phase; Osmolar Concentration; Pregnancy; Pregnancy Complications, Cardiovascular; Radioimmunoassay; Vasopressins

Topics: Aldosterone; Amino Acid Sequence; Animals; Blood Vessels; Heart Atria; Hypertension; Myocardium; Natriuresis; Natriuretic Agents; Proteins; Rabbits; Rats; Vasopressins

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Hypertension; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; Sodium; Spinal Cord; Vasopressins

The development of hypertension induced by deoxycorticosterone acetate (DOCA) in sheep was accompanied by increases in both the plasma concentration and the urinary excretion of vasopressin. The vasopressin response to an osmotic stimulus (i.v. infusion of 0.85 mol NaCl/l at 4 ml/min for 75 min) was studied before and after the development of hypertension induced by DOCA in six sheep. Before DOCA implantation, the osmotic stimulus resulted in an increase of plasma osmolality (POSM) from 290 +/- 1 to 303 +/- 1 (S.E.M.) mosmol/kg H2O and in plasma vasopressin concentration (PAVP) from 0.23 +/- 0.04 to 1.07 +/- 0.15 microunits/ml. At least 30 days after DOCA implantation when mean arterial blood pressure had risen from 81 +/- 3 to 117 +/- 5 mmHg, the same osmotic load caused an increase in POSM from 290 +/- 2 to 298 +/- 2 mosmol/kg H2O and PAVP from 0.45 +/- 0.05 to 2.02 +/- 0.27 microunits/ml. POSM and PAVP were significantly correlated in every experiment. However, the slope of the relationship increased significantly (P less than 0.01) after the animals had developed hypertension (0.185 +/- 0.026 vs 0.070 +/- 0.011 (microunits vasopressin/ml)/(mosmol/kg H2O]. The intercepts were similar. After the DOCA implant had been removed osmotic sensitivity returned to normal.

Topics: Animals; Desoxycorticosterone; Hypertension; Male; Osmolar Concentration; Osmotic Pressure; Sheep; Vasopressins

The effect of two consecutive hemorrhages, each 10% of blood volume, on plasma vasopressin concentrations was determined in conscious unilaterally nephrectomized Long-Evans rats made hypertensive by treatment for 3 wk with deoxycorticosterone (DOC) and substitution of 1% saline for drinking water (DOC-salt rats) or DOC alone (DOC rats) and in normotensive unilaterally nephrectomized rats drinking water (H2O rats) or saline (NaCl rats). In response to 20% hemorrhage, blood pressure decreased more (P less than 0.01) and plasma vasopressin increased less (P less than 0.01) in the DOC-salt rats than in the other groups. Under basal conditions, immunoreactive vasopressin was found in the platelets in NaCl, DOC, and DOC-salt rats (P less than 0.01) but not in H2O rats. Platelet vasopressin increased (P less than 0.05-0.01) in response to hemorrhage only in DOC-salt rats. In conclusion, the vasopressin response to hemorrhage in DOC-salt rats is impaired; platelet immunoreactive vasopressin is of little importance in normal rats but is increased by treatment with DOC and/or chronic salt loading; and platelet vasopressin increased in response to hemorrhage only in DOC-salt rats.

Topics: Animals; Blood Platelets; Blood Volume; Desoxycorticosterone; Hemorrhage; Hypertension; Male; Nephrectomy; Rats; Saline Solution, Hypertonic; Time Factors; Vasopressins

Three approaches to the evaluation of the central cardiovascular effects of vasopressin are briefly reviewed. These include assessment of cardiovascular regulation in Brattleboro rats, cardiovascular responses to central nervous system injections of vasopressin, and changes in central nervous system vasopressin content in spontaneous and induced hypertension. The studies indicate that vasopressin could participate in baroregulation by actions within the central nervous system, but they fail to clearly define the importance of vasopressin, if any, in this capacity.

Topics: Anesthesia, General; Animals; Blood Pressure; Brain; Brain Mapping; Brain Stem; Cardiovascular Physiological Phenomena; Desoxycorticosterone; Hypertension; Injections, Intraventricular; Rats; Rats, Brattleboro; Rats, Inbred WKY; Sodium Chloride; Vasopressins

Intracerebroventricular (ICV) injections of carbachol produced biphasic blood pressure responses consisting of initial vasodepression of short duration followed by a sustained pressor phase, which were accompanied by corresponding changes in sympathetic nerve activity in normotensive outbred-Wistar rats (NT) under urethane-anesthesia. In both normotensive Kyoto Wistar rats (WKY) and spontaneously hypertensive rats (SHR), on the other hand, carbachol elicited purely pressor responses, and accompanying sympathetic nerve activity was little affected. The magnitude of the pressor responses was larger in SHR than in WKY or NT rats. Spinal sectioning did not affect the magnitude of the pressor responses. Vasopressor responses to intravenous injections of arginine-vasopressin were not significantly different between WKY and SHR. These results indicate that carbachol injected intracerebroventricularly produces vasopressor effects mainly by releasing pituitary hormones, probably vasopressin, and that augmented pressor responses in SHR may be due to excessive release of vasopressin. When central noradrenergic neurons had been destroyed with ICV injections of 6-hydroxydopamine in both NT and WKY rats, carbachol-induced vasopressor responses were markedly augmented and resulted in responses similar to those of SHR. These findings indicate that central noradrenergic vasodepressive neurons are deficient and that the augmented vasopressor responses to carbachol resulted from deranged central noradrenergic mechanisms in SHR.

Topics: Animals; Blood Pressure; Brain; Carbachol; Heart Rate; Hemodynamics; Hydroxydopamines; Hypertension; Injections, Intraventricular; Male; Norepinephrine; Oxidopamine; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Receptors, Cholinergic; Spinal Cord; Sympathetic Nervous System; Vasopressins

Effect of chronic angiotensin converting enzyme blockade on the pressor response to exogenous angiotensin II, noradrenaline and vasopressin were evaluated in DOCA-salt induced hypertensive rats using teprotide. The blood pressure of rats receiving teprotide chronically was reduced markedly. The pressor responses to exogenous angiotensin II was accentuated, while that of noradrenaline and vasopressin were significantly reduced. It is concluded that besides the angiotensin converting enzyme blocking action, the decrease in sensitivity of the pressor response to noradrenaline and vasopressin may contribute towards the antihypertensive activity of teprotide given chronically.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Desoxycorticosterone; Hypertension; Male; Norepinephrine; Rats; Renin; Vasopressins

To assess the role of renal prostaglandin E in the hypotensive mechanism of MK-421, we evaluated the effects of chronic infusion of MK-421 (6 mg/kg/day i.p.) on systolic blood pressure and urinary prostaglandin E excretion in conscious rats in states of sodium repletion or depletion and also during chronic infusion of norepinephrine (1.8 mg/kg/day i.p.) or vasopressin (7.2 U/kg/day i.p.). The hypotensive effect of MK-421 was greater in sodium depleted than in sodium repleted rats. The hypertensive effect of norepinephrine or vasopressin was inhibited by the simultaneous administration of MK-421. MK-421 induced an increase in the excretion of urinary prostaglandin E, in both sodium repleted and depleted rats. However, simultaneous administration of MK-421 had no influence on the increase in urinary prostaglandin E excretion induced by norepinephrine or vasopressin. In addition, the combined administration of MK-421 with indomethacin (10 mg/kg/day s.c.) still abolished the hypertensive effect of norepinephrine or vasopressin. The disparate effect of MK-421 on urinary prostaglandin E excretion suggests that the renal prostaglandin system is not essential for the mechanism of the hypotensive effect of MK-421.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Biomechanical Phenomena; Blood Pressure; Consciousness; Dipeptides; Enalapril; Hypertension; Kidney; Male; Norepinephrine; Prostaglandins E; Rats; Rats, Inbred Strains; Sodium; Vasopressins

Arginine-vasopressin (AVP), the antidiuretic hormone, not only regulates water balance but may also exert direct and indirect effects on blood pressure by influencing systemic vascular resistance and body fluid volumes. Recently, specific competitive antagonists of AVP at its vascular and tubular receptors have been described. We used d(CH2)5Tyr(Me) AVP, a vascular (V1) antagonist, and d(CH2)5-D-Tyr(Et) VAVP, a vascular and tubular (V1V2) antagonist, for studies on the role of AVP in deoxycorticosterone acetate (DOCA)-salt hypertension. The antagonists were infused intravenously via osmotic minipumps in unilaterally nephrectomized rats for 6 weeks after the beginning of the DOCA-salt treatment. At the end of the experiment, blood pressure was 15 mm Hg lower in the rats receiving the V1 antagonist than in those in which the vehicle was infused. In the rats receiving the V1V2 antagonist, blood pressure was reduced by 38 mm Hg. However, these rats were in poor general condition and gained no body weight. Their plasma sodium concentration was markedly increased throughout the duration of the experiment. These results suggest that AVP contributes to the development of DOCA-salt hypertension not only through its vascular but also through its renal tubular effects. Thus AVP may act as an impormediator of volume changes associated with alterations in sodium intake or excretion and thereby affect blood pressure.

Topics: Animals; Body Water; Body Weight; Desoxycorticosterone; Endocrine Glands; Hematocrit; Hypertension; Male; Rats; Rats, Inbred Strains; Sodium; Vasopressins

The role of vasopressin as a pressor agent to the hypertensive process was examined. Vasopressin plays a major role in the pathogenesis of DOCA-salt hypertension, since the elevation of blood pressure was not substantial in the rats with lithium-treated diabetes insipidus after DOCA-salt treatment. Administration of DDAVP which has antidiuretic action but minimal vasopressor effect failed to increase blood pressure to the levels observed after administration of AVP. Furthermore, the pressor action of vasopressin appears to be important in the development of this model of hypertension, since the enhanced pressor responsiveness to the hormone was observed in the initial stage of hypertension. Increased secretion of vasopressin from neurohypophysis also promotes the function of the hormone as a pathogenetic factor in hypertension. An unproportional release of vasopressin compared to plasma osmolality may be induced by the absence of an adjusting control of angiotensin II forming and receptor binding capacity for sodium balance in the brain. However, the role of vasopressin remains to be determined in human essential hypertension.

Topics: Animals; Blood Pressure; Chlorides; Deamino Arginine Vasopressin; Desoxycorticosterone; Hypertension; Injections, Intravenous; Lithium; Lithium Chloride; Male; Rats; Receptors, Angiotensin; Salts; Vasopressins

Plasma antidiuretic hormone (ADH), PRA, plasma osmolality, and the parameters of renal water excretion were measured after overnight dehydration and for 5 h after an oral load in 14 patients with congestive heart failure (CHF) treated with diuretics (group 1), 8 hypertensive patients without CHF also treated with diuretics (group 2), and 11 patients with coronary artery disease but without CHF who were not treated with diuretics (group 3). Under basal conditions, mean plasma osmolality was lower in group 1 than in group 3, but was not different in groups 1 and 2. Mean plasma ADH was higher in group 1 than in group 2 or 3. In response to the water load, plasma osmolality and plasma ADH levels decreased in the 3 groups. ADH levels remained significantly greater in group 1 than in groups 2 and 3 from 2-4 h after the water load despite more marked hypoosmolality in group 1 compared with that in either of the 2 control groups. Plasma ADH was significantly correlated with plasma osmolality only in the 2 control groups. Mean PRA was greater in patients with CHF and patients without CHF treated with diuretics than in untreated patients. Cumulative water excretion was lower in patients with CHF than in patients in the 2 control groups from 2-5 h after the water load. At 5 h, the mean percentage excretion of the ingested loads was 56.8%, 90.7%, and 91.2% in the patients of groups 1, 2, and 3 respectively. Free water clearance was lower and minimal urinary osmolality was greater in the patients with CHF than in those in the 2 control groups. Two patients with CHF, who excreted more than 75% of the water load, also had low plasma basal ADH levels. These data show that patients with CHF have an inappropriate response of plasma ADH to a marked fall in plasma osmolality. This disorder is not due to the diuretic therapy, since hypertensive patients treated with diuretics behaved similarly to untreated patients without CHF. The reasons for this inappropriate response of plasma ADH during a water load in patients with CHF are probably multifactorial.

Topics: Adult; Body Water; Diuretics; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Osmolar Concentration; Renin; Vasopressins

A group of 89 individuals with essential hypertension was evaluated with several measurements including the neurophysin believed to be the human oxytocin neurophysin (OT-Np), and the human vasopressin neurophysin (VP-Np). The neurophysins are proteins synthesized within cells of the supraoptic and paraventricular nuclei in conjunction with their respective hormones oxytocin and vasopressin as part of a common precursor molecule and so may reflect the simultaneous presence in plasma of their associated hormones. A poor but statistically significant correlation was noted between levels of OT-Np and renin activity in plasma (PRA) either supine (r = 0.248) or erect (r = 0.255). Levels of OT-Np averaged 1.75 ng/ml and were inversely correlated with creatinine (r = -0.252), supine blood pressure (r = -0.450), plasma volume (r = -0.327), and 24-hour urine sodium (r = -0.313). Levels of Ot-Np could be suppressed by infusion of physiologic saline. Levels of OT-Np were lower in the volume expanded state and were positively correlated with the quantity of sodium excreted into a 24-hour urine collected after the infusion (r = 0.426) and inversely correlated with the supine systolic (r = -0.379) and supine diastolic (r = -0.455) blood pressures recorded after the infusion of saline. Oestrogen, a stimulus to the secretion of OT-Np, did not account for the elevation of OT-Np observed in the study, since mean levels of oestradiol (E2) in a subset of the patients with elevated OT-Np (E2 = 36 pg/ml) were not different from levels in subjects with lower values of OT-Np (E2 = 45 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Blood Pressure; Creatinine; Dopamine; Estradiol; Female; Humans; Hypertension; Male; Middle Aged; Neurophysins; Oxytocin; Plasma Volume; Posture; Renin; Sodium; Vasopressins

The effect of prolonged intracerebroventricular (i.c.v.) infusion of N-acetyl-pepstatin in young and adult spontaneously hypertensive rats was studied. In young animals, pepstatin infusion resulted in a decrease in blood pressure and heart rate. Water intake and body weight were not affected. The depressor effect was accompanied by a slight increase in plasma renin activity and decreases in plasma vasopressin and plasma catecholamines. The blood pressure of adult rats with already established hypertension was not significantly affected. In addition, changes in plasma renin or catecholamines were not observed in these animals while vasopressin levels were slightly increased. The involvement of a possibly decreased sympathetic activity in the depressor effect of pepstatin is suggested. It is concluded that increased brain renin activity contributes to the development of hypertension of spontaneously hypertensive rats.

Topics: Aging; Angiotensin I; Animals; Blood Pressure; Cerebral Ventricles; Heart Rate; Hypertension; Injections, Intraventricular; Kinetics; Male; Oligopeptides; Pepstatins; Rats; Renin; Renin-Angiotensin System; Vasopressins

The purpose of this note is to show that vasopressin might be involved in the hypoalgesia of the spontaneously hypertensive rat. This proposal rests upon published data.

Topics: Animals; Hypertension; Pain; Rats; Rats, Inbred Strains; Sensory Thresholds; Vasopressins

We have previously shown that high doses of leukotriene D4 (LTD4) induces hypotension in conscious and in pithed spontaneously hypertensive rats. The present study was designed to determine whether the hypotensive effect of LTD4 in spontaneously hypertensive rats is due to reduced sensitivity of peripheral blood vessels to pressor stimuli and/or reduced responsiveness of the sympatho-adrenomedullary system. To test these possibilities we examined the effect of spinal cord stimulation, vasopressin, norepinephrine and angiotensin II on blood pressure, heart rate and plasma catecholamines of pithed spontaneously hypertensive rats, before and after treatment with LTD4 (20 micrograms/kg i.v.), a dose which produces hypotension in conscious and pithed rats. LTD4 suppressed the pressor responses to spinal cord stimulation (50 V, 1 msec, for 1 min) at 0.3 and 3.0 Hz by 64% (P less than .001) and 71% (P less than .001), respectively, and the pressor and cardiac accelerating effects of systemic injections of norepinephrine. Plasma norepinephrine response to spinal cord stimulation at 3.0 Hz was significantly (P less than .05) reduced after administration of LTD4. The evoked release of epinephrine from the adrenal medulla was enhanced (+139%, P less than .05) by LTD4, but the tachycardia was blocked. The pressor responses to 0.1 and 1.0 microgram/kg of angiotensin II were blocked by 73% (P less than .05) and 70% (P less than .01), respectively. The pressor effects produced by vasopressin (0.03 and 0.1 microgram/kg) were also attenuated (by 83 and 80%, respectively) after LTD4 administration. The depressor effect of sodium nitroprusside (0.01-0.1 mg/kg) was also attenuated by LTD4. These data suggest that LTD4-induced hypotension involves severe interference with vascular smooth muscle responsiveness to all pressor agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Blood Pressure; Catecholamines; Decerebrate State; Electric Stimulation; Heart Rate; Hematocrit; Hypertension; Nitroprusside; Norepinephrine; Rats; Rats, Inbred SHR; Spinal Cord; SRS-A; Sympathetic Nervous System; Vasopressins

A study was carried out of the effects of iv angiotensin II on vasopressin release and the distribution of vasopressin between platelets and plasma in 12 week old conscious unrestrained SH and WKY rats. Angiotensin II was infused at rates of 31.25 to 500 ng/kg X min for 20 min. There was an enhanced pressor responsiveness to angiotensin II in the SH rats. Angiotensin II caused a moderate increase in plasma vasopressin concentrations, but only at doses which produced maximal pressor responses (250 to 500 ng/kg X min). There were no significant differences in vasopressin responses to angiotensin II in SH compared to WKY rats. Approximately 30% of circulating immunoreactive vasopressin was found in platelets in both SH and WKY rats, and this distribution was not greatly affected by the iv infusion of angiotensin II.

Topics: Angiotensin II; Animals; Blood Platelets; Blood Pressure; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasopressins

Topics: Blood Pressure; Catecholamines; Humans; Hypertension; Kinins; Prostaglandins; Renin-Angiotensin System; Vasopressins

There is evidence for an increased secretion of vasopressin in most models of hypertension, e.g., deoxycorticosterone (DOC)-salt hypertension, one- and two-kidney renal hypertension, partial nephrectomy-salt hypertension, the spontaneously hypertensive rat (SHR), the Dahl salt-sensitive rat on a high-salt diet, and human essential hypertension. In most forms of hypertension, there is also an increased pressor responsiveness to vasopressin as well as to other pressor agents. Blockade of vasopressin with either a competitive antagonist or a specific antiserum lowered blood pressure substantially in DOC-salt hypertension, two-kidney, one-clip hypertension, the stroke-prone SHR with well-established hypertension, and the Dahl S rat treated with captopril. In rats with diabetes insipidus, one- and two-kidney renal hypertension, but not DOC-salt hypertension, can be produced. There is evidence that vasopressin can contribute to some models of hypertension as either a pressor or an antidiuretic agent.

Topics: Animals; Desoxycorticosterone; Disease Models, Animal; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Nephrectomy; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Species Specificity; Vasopressins

Infusions of carbachol into the posterior region of the 3rd ventricle of rats for 7 days produced a sustained elevation of blood pressure and heart rate at doses of 0.6 and 1.2 microgram/hr, but only transient rises in blood pressure were obtained at 2.4 microgram/hr. Carbachol, at 0.6 microgram/hr, increased water consumption. At 1.2 microgram/hr, the dipsogenic effect was observed in 50% of the animals and at 2.4 microgram/hr there was no significant change in drinking. Plasma vasopressin levels, measured by radioimmunoassay, were increased by 19-fold 3 min after acute i.c.v. administration of carbachol (0.5 microgram/rat). However, in rats infused with carbachol for 2 or 5 days, the vasopressin levels were not significantly different from controls. The pressor responses to acute and chronic administration of carbachol could be ascribed to the stimulation of periventricular muscarinic receptors because the effects were blocked by atropine, but not by hexamethonium. In carbachol-infused animals, the pressor responsiveness to i.v. norepinephrine and vasopressin were unchanged. From studies using phentolamine, chlorisondamine and a specific vasopressin vasopressor antagonist, it could be inferred that the pressor responses to acute i.c.v. injections of carbachol were due to increased sympathetic activity and vasopressin release. However, the sustained hypertension produced by chronic infusion of carbachol was due primarily to increased sympathetic activity and not to increased plasma levels of vasopressin.

Topics: Animals; Blood Pressure; Carbachol; Drinking; Female; Heart Rate; Hypertension; Injections, Intraventricular; Pressoreceptors; Rats; Rats, Inbred Strains; Receptors, Muscarinic; Sympathetic Nervous System; Vasopressins

The roles of arginine vasopressin (AVP), the sympathetic nervous system, and the renin-angiotensin system in maintaining elevated blood pressure in established DOC-salt hypertension in rats were studied by injection of specific antagonists of these systems. The specific AVP antagonist dPVDAVP decreased blood pressure by 19 +/- 3 mm Hg in hypertensive rats and 6 +/- 2 mm Hg in control rats. In a different group of rats ganglionic blockade with chlorisondamine also caused a greater decrease in blood pressure in DOC-salt rats compared to controls (99 +/- 6 vs 58 +/- 4 mm Hg, respectively). In rats with autonomic ganglia blocked subsequent vasopressin antagonism decreased blood pressure 29 +/- 4 mm Hg in DOC-salt rats and 14 +/- 2 mm Hg in control rats. Converting enzyme inhibition with captopril in rats with autonomic ganglia blocked caused a lesser decrease in blood pressure in DOC-salt rats than in controls (8 +/- 2 vs 14 +/- 2 mm Hg, respectively). These results indicate that both AVP and the sympathetic nervous system contribute to the maintenance of DOC-salt hypertension. The renin-angiotension system appears to be relatively less important.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Female; Hypertension; Male; Nephrectomy; Rats; Renin-Angiotensin System; Sodium Chloride; Sympathetic Nervous System; Vasopressins

A number of experiments were performed in order to investigate the possible importance of vasopressin (AVP) in the pathogenesis of high blood pressure in spontaneously hypertensive rats of the stroke prone strain (SHRSP). Radioimmunological studies revealed reduced concentrations of AVP in the plasma and brain of SHRSP as compared to normotensive controls. Intravenous administration of an AVP pressor antagonist had no significant influence on mean arterial blood pressure, cardiac output and total peripheral resistance in SHRSP. Crossbreeding of SHRSP with rats homozygous for hypothalamic diabetes insipidus resulted in the development of a new strain of rats which show high blood pressure despite of a complete lack in AVP. These results argue strongly against a pressor role of AVP in the development or maintenance of hypertension in SHRSP.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Brain Chemistry; Hypertension; Male; Oxytocin; Rats; Rats, Inbred Strains; Vasopressins

In conscious spontaneously hypertensive rats, pergolide (50.0 micrograms/kg s.c.) produced a sustained decrease in tail artery pressure which was blocked by haloperidol (1.0 mg/kg s.c.) pretreatment. In anesthetized spontaneously hypertensive rats this effect was accompanied by a fall in total peripheral resistance inasmuch as pergolide did not significantly change cardiac output. In anesthetized normotensive rats, pergolide (30.0 micrograms/kg i.v.) also lowered blood pressure. This effect was not significantly modified by adrenalectomy, methysergide, idazoxan (alpha-2 adrenoceptor antagonist), vagotomy alone or plus ligation of carotid arteries or plus atenolol, but was entirely prevented by domperidone or sulpiride pretreatment and was reverted to a pressor response (due to stimulation of alpha adrenoceptors and 5-hydroxytryptamine receptors) by blockade of ganglionic transmission with chlorisondamine. Pergolide given either i.v. or into the cisterna magna or the lateral cerebral ventricle produced changes in blood pressure of the same magnitude. In intact or adrenalectomized rats, i.v. pergolide significantly lowered plasma norepinephrine concentration. Furthermore, in saline but not sulpiride-pretreated pithed rats, pergolide reduced the pressor responses and the accompanying increases in plasma norepinephrine evoked by electrical stimulation of the spinal cord. However, pergolide failed to modify the vascular reactivity to several pressor agents and lacked beta-2 and DA-1 dopamine receptor agonist properties. These results indicate that the decrease in blood pressure produced by pergolide can be accounted for by an inhibition of sympathetic tone resulting from stimulation of peripheral neuronal dopamine receptors. A possible central contribution remains to be substantiated. The pronounced bradycardia produced by pergolide (30.0 micrograms/kg i.v.) in anesthetized intact rats was partly reduced by vagotomy, methylatropine, domperidone, sulpiride, idazoxan, phentolamine or atenolol. The effects of pergolide in vagotomized rats were further diminished by domperidone but they were blocked by the combination of phentolamine or idazoxan plus domperidone. In rats pretreated with atenolol or in rats with the cervical section of spinal cord and the low level of heart rate increased with an isoprenaline infusion, the decrease in heart rate produced by pergolide was abolished by domperidone, methylatropine or idazoxan. In pithed rats, pergolide changed neither

Topics: Adrenalectomy; Animals; Antiparkinson Agents; Autonomic Nervous System; Blood Pressure; Clonidine; Decerebrate State; Dose-Response Relationship, Drug; Ergolines; Heart Rate; Hypertension; Male; Methysergide; Norepinephrine; Pergolide; Phenoxybenzamine; Rats; Rats, Inbred Strains; Receptors, Dopamine; Spinal Cord; Vascular Resistance; Vasopressins

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Hypertension; Lypressin; Male; Phentolamine; Propranolol; Rats; Rats, Inbred Strains; Vasopressins

The influence of tetrandrine on arterial pressure and heart rate of pentobarbitone-anaesthetized and conscious normotensive and hypertensive rats (SH rats, renal hypertensive rats, DOCA-salt hypertensive rats) was investigated. Tetrandrine administered intravenously (i.v.) to these animals caused an acute, long-lasting and dose-dependent decrease in mean arterial pressure. Heart rate was not significantly altered. In pithed rats, tetrandrine injected intraarterially 15 min previously impaired the increase in diastolic pressure induced by i.v. B-HT 920, a highly selective alpha 2-adrenoceptor-stimulating agent, in a dose-dependent manner. In a low dose, a parallel displacement to the right was observed, whereas for higher doses the shift was non-parallel. A high dose of tetrandrine shifted the pressor response curve of the alpha 1-adrenoceptor agonist, methoxamine, only slightly to the right and did not depress the maximal response. Tetrandrine also caused a moderate rightward shift of the vasopressor effect curve of vasopressin applied i.v. Tetrandrine displayed only minor affinities for specific binding sites in rat brain membranes for [3H]-prazosin (alpha 1-adrenoceptors) and for [3H]-clonidine (alpha 2-adrenoceptors). The results obtained suggest that the hypotensive effect of tetrandrine may be related to an impairment of vasoconstrictor tone mediated by vascular postsynaptic alpha 2-adrenoceptors.

Topics: Alkaloids; Anesthesia; Animals; Antihypertensive Agents; Azepines; Benzylisoquinolines; Blood Pressure; Brain; Clonidine; Heart Rate; Hypertension; Male; Methoxamine; Prazosin; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Vasopressins

Topics: Adult; Aged; Angiotensin II; Angiotensinogen; Angiotensins; Blood Pressure; Captopril; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Proline; Renin; Time Factors; Vasopressins

In order to investigate the antidiuretic hormone (ADH) in essential hypertension and secondary hypertension, plasma ADH levels were measured in normal subjects, in patients with normal and low essential hypertension, and in other patients with various forms of secondary hypertension. Plasma ADH levels were significantly lower in low renin essential hypertension and higher in malignant hypertension than in normal subjects. The plasma ADH levels tended to be lower in renal hypertension and primary aldosteronism, and higher in renovascular hypertension, but these differences were not statistically significant. From these results, it appeared that ADH might play a role in malignant hypertension, but not in the other hypertensive diseases.

Topics: Adolescent; Adult; Aged; Female; Humans; Hypertension; Male; Middle Aged; Renin; Vasopressins

The management of lower gastrointestinal bleeding has evolved from a number of technological advances allowing precise diagnosis and localization of the bleeding site. This study of 40 angiographically demonstrated lower gastrointestinal bleeding lesions reinforces much of the data indicating the diagnostic and therapeutic trends. Twenty-four patients had bleeding diverticula with angiographic demonstration in 11 patients. Seven cases of vascular ectasia were identified, and nine patients had a variety of significant bleeding sites other than the two main sites that were listed. Pitressin was useful for control of bleeding in six of seven diverticular patients but was less useful in the vascular ectasia group in which only one patient was actively bleeding. Total abdominal colectomy and segmental resection were successful in control of hematochezia in 24 of 25 operative cases. Sixteen patients did not require surgical treatment.

Topics: Aged; Angiography; Arginine Vasopressin; Colectomy; Diverticulum, Colon; Diverticulum, Stomach; Female; Gastrointestinal Hemorrhage; Humans; Hypertension; Male; Middle Aged; Vasopressins

A 54-year-old woman had seizures and a focal neurologic deficit associated with hyponatremia induced by a thiazide diuretic. Prompt correction of hyponatremia by administration of hypertonic saline solution was followed by resolution of all neurologic defects. Metabolic balance studies and rechallenge with hydrochlorothiazide were undertaken to investigate the mechanism of the thiazide-induced hyponatremia. Abnormal vasopressin secretion was shown by a plasma vasopressin concentration of 0.5 microU/ml with a plasma osmolality of 268 mOsm/kg water after administration of a fluid challenge consisting of 45 ml/kg body weight. Rechallenge with chlorothiazide while on a sodium- and potassium-controlled balanced diet resulted in a decrease in serum sodium concentration (136 to 124 mEq/L) and plasma osmolality (283 to 261 mOsm/kg) within 18 hours. During this period, urine losses of monovalent cation were only 55 mEq and body weight was constant at 48.2 kg. A second challenge while the patient received all fluids and electrolytes intravenously again resulted in decreased serum sodium concentration (134 to 126 mEq/L) after urinary loss of only 69 mEq of cation. Thus this patient's hyponatremia cannot be accounted for solely by changes in external water and electrolyte balance; the rapidity with which changes were produced suggests that osmolar inactivation, probably intracellularly, may contribute to the severe hypotonicity seen in some patients.

Topics: Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Hyponatremia; Middle Aged; Neurologic Manifestations; Osmolar Concentration; Recurrence; Seizures; Sodium; Triamterene; Vasopressins

Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.

Topics: Adult; Aldosterone; Blood Pressure; Electrolytes; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Mineralocorticoids; Regression Analysis; Sodium; Vasoconstriction; Vasopressins

Plasma vasopressin levels were compared in three groups comprising normotensive, mildly hypertensive, and more severely hypertensive patients, both under basal conditions and following an 85 degrees head-up tilt, a stimulus known to provoke vasopressin release in man. Vasopressin levels increased two- to fivefold in all subjects after tilt; however, neither the basal levels nor the maximal levels attained at 45 to 60 minutes after tilt differed in the three groups. These data do not support the postulated role for vasopressin in the causation or perpetuation of non-accelerated essential hypertension in man.

Topics: Adult; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Posture; Vasopressins

An 8-yr-old girl is presented who had periodic attacks of vomiting, psychotic depression, drowsiness, and hypertension (160/110 mm Hg) for a period of 16 months after head injury. At the initiation of the attack, serum ACTH and vasopressin levels were prominently increased (610 pg/ml and 41 microunits/ml, respectively), followed by hypercortisolemia, hyponatremia, and hypoosmolality in plasma. Serum PRL also was elevated (91 ng/ml). Responses of GH and cortisol to insulin-induced hypoglycemia and those of TSH to TRH were reduced. Urinary excretion of epinephrine and norepinephrine were increased, while dopamine (DA) excretion was reciprocally decreased, resulting in a marked elevation of the epinephrine plus norepinephrine to DA ratio during the episodes (0.4-4.5); this was normalized on attack-free days (0.08-0.25). During the attack, the concentration of homovanillic acid, a major metabolite of DA in the brain, also was reduced in cerebrospinal fluids from 70 to 23 ng/ml. The administration of methyl-dopa and reserpine effectively suppressed the recurrence of the episode. Although the exact cause of this syndrome is unknown, a periodic metabolic dysfunction of catecholamine in the central nervous system might be postulated.

Topics: Adrenocorticotropic Hormone; Brain Concussion; Catecholamines; Child; Female; Humans; Hypertension; Insulin; Methyldopa; Periodicity; Pituitary Hormones, Anterior; Prolactin; Reserpine; Syndrome; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins; Vomiting

The corticotropic function of the adenohypophysis was investigated in patients with essential hypertension considering the stage of the disease and development of crisis. There was found functional activation of the system under study at the labile stage of essential hypertension without crisis as well as in patients with crisis at labile and stable stages of the disease. Unidirectional shifts were observed in the function of the vasopressor part of the hypothalamus-neurohypophyseal system.

Topics: Adrenocorticotropic Hormone; Adult; Humans; Hydrocortisone; Hypertension; Vasopressins

Topics: Adrenocorticotropic Hormone; Adult; Aldosterone; Humans; Hypertension; Obesity; Renin; Secretory Rate; Vasopressins

To determine if the increased vasopressin (AVP) levels observed in the blood and urine of spontaneously hypertensive rats (SHR) are a response to peripheral factors that may influence AVP release or are a consequence of altered hypothalamic-neurohypophysial activity, AVP release from hypothalamic-neurohypophysial units was studied using an in vitro perifusion system. Spontaneous and 30 mM K+-stimulated AVP release was significantly greater from tissue of SHR rats than from those of WKYN. Adenosine (10(-5) M) added to the perifusion medium increased AVP release into the perifusate in both strains, even through AVP release into the perifusate was greater in tissue of SHR rats. Measurement of AVP content revealed that hypothalamic AVP was lower in SHR rats, whereas the neural lobes of the SHR contained a significantly higher concentration of AVP compared to the tissue of WKYN rats. In addition, exposing tissue from SHR rats to 30 mM K+ stimulated an increase in cAMP release into the perifusate, whereas tissue from WKYN rats did not increase cAMP release above basal level. These data suggest that central nervous system-mediated hyperresponsiveness is the basis for the increased AVP secretion that occurs in the SHR rat and are consistent with reports of a hypersensitive hypothalamic-anterior pituitary axis in these animals.

Topics: Animals; Cyclic AMP; Female; Hypertension; Hypothalamus; Male; Pituitary Gland, Posterior; Potassium; Rats; Rats, Inbred Strains; Time Factors; Vasopressins

Topics: Biological Transport; Blood Pressure; Calcium; Erythrocyte Membrane; Humans; Hypertension; Potassium; Sodium; Sodium-Potassium-Exchanging ATPase; Vasopressins

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Kidney; Male; Norepinephrine; Rats; Rats, Brattleboro; Rats, Mutant Strains; Sodium Chloride; Vascular Resistance; Vasopressins

Topics: Animals; Arginine Vasopressin; Cerebral Ventricles; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Male; Rats; Rats, Brattleboro; Rats, Inbred Strains; Rats, Mutant Strains; Sodium Chloride; Vasopressins

Topics: Aldosterone; Blood Pressure; Blood Volume; Captopril; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Potassium; Proline; Renin; Renin-Angiotensin System; Sodium; Vasopressins; Water-Electrolyte Balance

1. Arginine vasopressin was infused at 0.5, 2, 6, 18 or 54 ng min(-1) kg(-1) for 1 hr into normal, sham-operated and DOCA-salt hypertensive rats. Complete vasopressin/blood pressure dose-response curves were constructed from circulating plasma vasopressin concentrations measured at the end of each infusion. 2. DOCA-salt hypertensive rats had a higher basal plasma vasopressin concentration (11.1 +/- SD 3.7 fmol/ml) than either the normal (3.9 +/- 2.3, P less than 0.01) or the sham-operated rats (4.5 +/- 2.4, P less than 0.01). 3. The DOCA-salt hypertensive rats did not have my detectable enhancement of pressor sensitivity, compared with either of the two normotensive groups. 4. There was no significant increase in blood pressure in either the normal rats or sham-operated rats until vasopressin was infused at 2 ng min(-1) kg(1), when the plasma concentration was between 30 and 40 fmol/ml. 5. Subpressor infusion of vasopressin in the normal and sham-operated rats, which gave plasma concentrations of 22-23 fmol/ml, completely suppressed plasma angiotensin II to levels similar to the basal values found in the DOCA- salt hypertensive rats (10.5 +/- 2.3, 14.5 +/- 4.5 and 8.0 +/- 1.6 fmol/ml respectively). 6. These findings suggest that the mechanism of vasopressin involvement in DOCA-salt hypertension is as yet unclear, that short-term changes in vasopressin concentration appear unimportant in the regulation of normal blood pressure, that small physiological changes of vasopressin in normal rats may be important in the regulation of renin secretion, and that the increase in vasopressin concentration seen in DOCA-salt hypertension may contribute to the suppression of renin and angiotensin II in this state.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Dose-Response Relationship, Drug; Hypertension; Male; Rats; Rats, Inbred Strains; Vasopressins

Topics: Animals; Autonomic Nervous System; Blood Pressure; Desoxycorticosterone; Drug Interactions; Hypertension; Male; Rats; Rats, Inbred Strains; Sodium; Vascular Resistance; Vasopressins

A series of experiments was designed to explore the mechanisms contributing to hypertension caused by an acute or chronic sodium load. Acute salt-loading in totally or subtotally nephrectomized animals caused hypertension mediated partly through stimulation of excessive vasopressin release and partly through adrenergic stimulation. Chronic high-salt diet in rats submitted to partial nephrectomy, mineralocorticoid excess or one-kidney-one-clip renovascular hypertension caused blood pressure elevation mediated through a central neurogenic mechanism that could be reversed by administration of an inhibitor of phenylethanolamine-N-methyltransferase, the enzyme catalyzing conversion of norepinephrine to epinephrine. Thus, two vasopressor mechanisms were stimulated by sodium excess: an acute, transient, partly vasopressin-mediated phase seemed to be followed by a chronic phase mediated through stimulation of central sympathetic neurons. In neither phase was blood pressure related to intravascular fluid volume expansion.

Topics: Animal Feed; Animals; Diet, Sodium-Restricted; Hypertension; Nephrectomy; Phenylethanolamine N-Methyltransferase; Plasma Volume; Rats; Sodium; Sympathetic Nervous System; Vasopressins

Topics: Animals; Arginine Vasopressin; Autonomic Nervous System; Blood Pressure; Brain; Cardiac Output; Feedback; Hemodynamics; Humans; Hypertension; Hypertension, Renovascular; Models, Neurological; Pressoreceptors; Reflex; Spinal Cord; Vascular Resistance; Vasopressins

Topics: Aged; Body Water; Diuretics; Humans; Hydrochlorothiazide; Hypertension; Hyponatremia; Male; Sodium Chloride Symporter Inhibitors; Vasopressins

Topics: Animals; Hypertension; Hypothalamus, Anterior; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Suprachiasmatic Nucleus; Supraoptic Nucleus; Vasopressins

On isolated arteriole preparations vasopressin behaves as an extremely potent vasoconstrictor. In healthy animals and man its pressor effect is counteracted by several compensatory mechanisms, including stimulation of the baroreceptor reflex with reduction of sympathetic activity, decrease in renin secretion, sodium loss and reduction of vascular response to vasopressor agents. Alterations of these mechanisms unmask the hypertensive effect of vasopressin as shown by several experimental hypertension models in animals. In human pathology vasopressin has been shown to be a good indicator of the severity pf arterial hypertension, but its role in that disease will only be determined when vascular antagonists of vasopressin devoid of paryial agonistic activity become available.

Topics: Animals; Blood Pressure; Blood Volume; Cats; Disease Models, Animal; Dogs; Hemodynamics; Homeostasis; Humans; Hypertension; Rabbits; Rats; Vasoconstriction; Vasopressins

Norepinephrine and epinephrine concentrations in the caudal and rostral part of the nucleus tractus solitarii (NTS) and in locus coeruleus (LC) of Sabra hypertension prone (SBH) rats are 2-4-fold higher than in the parent Sabra (SB) strain; SB rats have higher concentrations than the Sabra hypertension resistant (SBN) rats. Dopamine concentrations were higher in SBH as compared to SB and SBN rats only in the caudal NTS. Vasopressin concentrations in the NTS of SBH were 3-fold higher than the levels found in SB or SBN rats. These data suggest that catecholamines and vasopressin in specific brainstem nuclei are involved in either the pathogenesis or central response to hypertension in SBH rats.

Topics: Animals; Epinephrine; Hypertension; Locus Coeruleus; Male; Medulla Oblongata; Norepinephrine; Rats; Rats, Inbred Strains; Vasopressins

Topics: Animals; Blood Pressure; Desoxycorticosterone; Electric Stimulation; Female; Hypertension; Male; Norepinephrine; Rats; Vasoconstriction; Vasopressins

Hypothalamic and neurophypophyseal levels of catecholamines and peptides were measured in spontaneous and deoxycorticosterone (DOCA)/salt hypertension. Catecholamines, norepinephrine, epinephrine and dopamine were measured by electrochemical detection while the peptides, vasopressin, oxytocin, luteinizing hormone-releasing hormone (LHRH), the enkephalins and somatostatin (SRIF) were measured by radioimmunoassay. Blood pressure was significantly elevated in both groups as compared to their controls. Marked changes in central neural peptides were observed in the SHR, while no differences were seen in DOCA/salt hypertension. Hypothalamic vasopressin, oxytocin, LHRH and SRIF were significantly decreased. In the posterior pituitary, enkephalins were increased twofold in the SHR. With regard to catecholamines, there was no change in hypothalamic content. However, a dramatic decrease in neurohypophyseal dopamine was observed in SHR. Plasma levels of vasopressin were significantly elevated in both types of hypertension while oxytocin was increased only in the DOCA/salt model. These result show that (1) a wide spectrum of neuroendocrine changes are associated with genetic hypertension, (2) there are CNS differences between DOCA/salt and spontaneous hypertension, and (3) central aminergic changes may be involved in th neuroendocrine alterations seen in the SHR.

Topics: Animals; Blood Pressure; Catecholamines; Desoxycorticosterone; Endorphins; Enkephalins; Gonadotropin-Releasing Hormone; Hypertension; Hypothalamo-Hypophyseal System; Male; Oxytocin; Rats; Sodium Chloride; Somatostatin; Vasopressins

Plasma concentrations and urinary excretion rate of vasopressin (VP) were examined in ten cases of severe hypertension before and during short-term treatment by Captopril (SQ 14225). Before Captopril, plasma and urinary VP were high (respectively 5.24 pmol/l and 68 pmol/day) and positively correlated to plasma renin activity (PRA) and plasma aldosterone (PA). The decline in blood pressure (mean -15%) after Captopril was correlated not only to initial PRA and PA values, but also to plasma (r = 0.89; P less than 0.001) and urinary (r = 0.78; P less than 0.01) VP values. The initial dose of Captopril (1 mg/kg) induced a rapid decrease in blood pressure whereas plasma VP did not rise and aldosterone decreased. At the eighth day of Captopril treatment (mean daily dose 6 +/- 1.5 mg/kg) the drop in blood pressure (-12%) and in aldosterone persisted together with a significant reduction in plasma (1.18 pmol/l; P less than 0.01) and urinary (25 pmol/day; P less than 0.01) VP. It is suggested that these sustained simultaneous reductions in the rates of secretion of vasopressin and aldosterone are both elements of the antihypertensive effect of Captopril.

Topics: Adolescent; Adult; Aldosterone; Blood Pressure; Captopril; Female; Humans; Hypertension; Male; Middle Aged; Proline; Renin; Vasopressins

This paper reviews recent information about neural and humoral control of arterial blood pressure. Considerable evidence is accumulating in support of the concept that neural and humoral systems interact at both central and peripheral sites to modulate arterial pressure and to participate in the mechanisms of hypertension. The neural mechanisms reviewed include reflexes originating from sinoaortic receptors, and afferents arising from the kidney. Humoral agents discussed include angiotensin and vasopressin and the participation of their central and peripheral actions in the pathogenesis of hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Hormones; Humans; Hypertension; Neurons; Pressoreceptors; Reflex; Renin; Vasopressins

Plasma antidiuretic hormone (ADH) was measured before and after furosemide administration in hypertensive patients (essential benign hypertensions with low plasma renin activity) and in normal subjects. Furosemide-induced reduction of plasma volume was about 10% after 2 hours. In normal subjects, plasma ADH rose progressively till the end of the study (1.5 pg/ml per hour corresponding to about 3 pg/ml per liter of plasma water lost) whereas it remained unchanged in hypertensive patients. There was an early increase of plasma renin activity (PRA) in normal subjects followed by a progressive fall. PRA response was blunted in hypertensive patients. These results show that volume-dependent ADH secretion is inhibited in patients with essential benign hypertension.

Topics: Adult; Female; Furosemide; Humans; Hypertension; Male; Middle Aged; Plasma Volume; Renin; Vasopressins

The role of vasopressin in the pathogenesis of partial nephrectomy (PN)-salt hypertension was examined in the rat. Hypertension was produced by reducing renal mass 70% and substituting 1% saline for drinking water 2 to 4 days after surgery. PN alone resulted in an increase in systolic blood pressure. Subsequent salt loading led to a further large increase in arterial pressure. On the second to third day after substitution of saline for drinking water, urinary vasopressin excretion (UADHV) was increased six-fold and the plasma vasopressin concentration was increased two and one-half-fold. UADHV then fell to a level that was three-fold greater than control values 5 days later. Although there was a marked stimulation of vasopressin release during the period of salt loading, a vasopressin pressor antagonist had only a small effect on arterial pressure. This suggests vasopressin is not a major pressor agent in PN-salt hypertension.

Topics: Animals; Blood Pressure; Body Weight; Disease Models, Animal; Hypertension; Male; Nephrectomy; Rats; Sodium Chloride; Vasopressins

A study was undertaken to evaluate the role of vasopressin in the pathogenesis of hypertension in New Zealand genetically hypertensive (NZGH) rats. During the course of development of hypertension in NZGH rats from 4 to 11 weeks of age, the 24 h urinary excretion of vasopressin did not differ from that of the New Zealand normotensive control rats (NZNR). Furthermore, at the conclusion of the study (rats 13 to 14 weeks old), the plasma vasopressin concentrations in NZGH and NZNR rats were not significantly different. Although there was no evidence for a difference in secretion of vasopressin from the neurohypophysis in the NZGH rats, there was a substantially increased pressor responsiveness to vasopressin in these rats. This was not specific since NZGH rats also had an increased pressor responsiveness to angiotensin II. The importance of increased pressor responsiveness to vasopressin in the hypertensive process in the NZGH rat requires further study.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Hematocrit; Hypertension; Male; Potassium; Rats; Rats, Inbred Strains; Reference Values; Sodium; Species Specificity; Vasopressins

The further role of vasopressin in the pathogenesis of hypertension was studied in two different types of hypertensive rats in which the intravenous injection of a vasopressin antiserum reduced arterial blood pressure substantially. The increased secretion of vasopressin was demonstrated in deoxycorticosterone acetate (DOCA)-salt hypertensive and spontaneously hypertensive rats with high salt intake. Angiotensin II binding of the brain receptor which has been postulated to modify osmotically stimulated vasopressin release from neurohypophysis was not affected by sodium balance in these types of hypertensive rats, whereas the decrease in the brain receptor binding of angiotensin II was observed in the control rats. The lack of the adjusting control system in the brain angiotensin II receptors for sodium balance may be, at least in a part, responsible for the enhancement of vasopressin secretion in the hypertensive rats compared to that in the control rats with high salt intake. Since pressor responsiveness to vasopressin was increased in the rats with DOCA-salt hypertension, vasopressin may function as a direct pressor agent in the maintenance of high blood pressure in this type of hypertension.

Topics: Angiotensin II; Animals; Blood Pressure; Brain; Desoxycorticosterone; Hypertension; Male; Osmolar Concentration; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Sodium; Vasopressins

Topics: Animals; Dogs; Hemodynamics; Homeostasis; Humans; Hypertension; Muridae; Vasopressins

Topics: Adult; Female; Hemodynamics; Humans; Hypertension; Hypertension, Malignant; Male; Vasopressins

Catecholamine and vasopressin content were studied in discrete brain nuclei of the Sabra strain of hypertension prone (SBH) and resistant (SBN) rats. Higher concentrations of dopamine, norepinephrine and epinephrine were observed in the median eminence of SBN compared to SBH or controls (SB) rats. Dopamine and epinephrine levels were higher in the lateral septal nucleus of SBH rats as compared to SBN or SB. Vasopressin content in discrete regions along the hypothalamo-pituitary axis was elevated in both SBH and SBN as compared to SB, but were especially elevated in the SBH group. The catecholamine and vasopressin changes found in SBH are different than those described in other genetically hypertensive rats indicating a difference in either the pathogenesis or central response to hypertension of this strain.

Topics: Animals; Brain Chemistry; Catecholamines; Corpus Striatum; Disease Susceptibility; Hypertension; Hypothalamus; Limbic System; Male; Pituitary Gland; Rats; Vasopressins

The present study was conducted to measure norepinephrine release during sympathetic nerve stimulation and to evaluate vascular reactivity in the isolated perfused mesenteric vasculature of normotensive and Doca-salt hypertensive rats. Significantly greater vasoconstrictor responses to periarterial nerve stimulation, norepinephrine, and vasopressin, but not to barium chloride, were observed in the mesenteric vasculature of the hypertensive rats in comparison with the control normotensive group. Norepinephrine release, measured as total tritium overflow, during periarterial nerve stimulation at 4 Hz for 2 min, was identical in both normotensive and hypertensive animals. Phentolamine (5.3 micro M) significantly increased tritium overflow, but to the same extent in the normotensive and the hypertensive mesenteric vasculature, suggesting that the negative feedback presynaptic alpha-adrenoceptor mechanism, which has been proposed to modulate transmitter release, was unaltered in this form of hypertension. These results indicate that hyperresponsiveness of the mesenteric vasculature to periarterial nerve stimulation in the hypertensive rats is due to increased sensitivity of the vascular alpha-adrenoceptor and not facilitation of the transmitter release. The increased vascular reactivity to norepinephrine and vasopressin may be involved in the maintenance of Doca-salt hypertension.

Topics: Animals; Desoxycorticosterone; Electric Stimulation; Hypertension; Male; Norepinephrine; Phentolamine; Rats; Receptors, Adrenergic, alpha; Sympathetic Nervous System; Vasomotor System; Vasopressins

1. Neurosecretion of peptides from superfused neurohypophyses in vitro was inhibited by dopamine. 2. This inhibition was dose-dependent. 3. Intravenous injection of the dopamine agonist, bromocriptine, lowered blood pressure in spontaneously hypertensive rats within 15 min. 4. Saralasin or captopril also lowered blood pressure of spontaneously hypertensive rats, but progressively over a period of 3 h. 5. The results suggest that dopamine and angiotensin have opposite effects on the neurosecretion of vasopressin. 6. Vasopressin appears to be involved in maintenance of blood pressure in the spontaneously hypertensive rat but is apparently not the only factor.

Topics: Angiotensin II; Animals; Bromocriptine; Captopril; Dopamine; Hypertension; In Vitro Techniques; Oxytocin; Pituitary Gland, Posterior; Proline; Rats; Saralasin; Swine; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Desoxycorticosterone; Dose-Response Relationship, Drug; Hypertension; Kidney; Male; Nephrectomy; Norepinephrine; Rats; Vascular Resistance; Vasopressins

Vascular resistance and reactivity were investigated in isolated, constant flow perfused kidneys of stroke-prone spontaneously hypertensive rats (SHRSP) and age- and sex-matched normotensive Wistar-Kyoto control rats (WKY rats). Stroke-prone spontaneously hypertensive rats were studied at 4 wk, 2 mo, and 4 mo of age representing different stages of development of hypertension. Resistance in maximally vasodilated vascular beds was greater and the pressure-flow relationship was significantly shifted to the left in kidneys of SHRSP as compared to WKY rats. Responses to norepinephrine, vasopressin, serotonin, and angiotensin II were enhanced in the renal vascular bed of SHRSP. Dose-response curves were shifted to the left, had steeper slopes, decreased thresholds, and increased maximal responses. With longer duration of hypertension, resistance increased, the slopes of the dose-response curves were steeper, and maximum responses greater. The higher resistance and enhanced reactivity in the renal vasculature of SHRSP, already demonstrable in the prehypertensive stage appear to be due to primary structural and functional alterations of the resistance vessels.

Topics: Aging; Angiotensin II; Animals; Dose-Response Relationship, Drug; Hypertension; In Vitro Techniques; Kidney; Male; Muscle, Smooth, Vascular; Norepinephrine; Rats; Serotonin; Vascular Resistance; Vasopressins

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Hypertension; Intestinal Mucosa; Intestines; Mesenteric Arteries; Mesenteric Vascular Occlusion; Oxygen Consumption; Regional Blood Flow; Vasopressins; Venous Pressure

In patients with essential hypertension the blood antidiuretic activity was studied in relation to the haemodynamics. It was found that the blood antidiuretic activity increased in parallel with the rise in the total peripheral resistance, and with the decreases in the blood and plasma volumes, stroke volume, and end-diastolic heart volume. The role of antidiuretic hormone in the regulation of haemodynamics in hypertensive patients is discussed.

Topics: Adult; Blood Volume; Cardiac Output; Cardiac Volume; Hemodynamics; Humans; Hypertension; Pulmonary Circulation; Stroke Volume; Vascular Resistance; Vasopressins

Normotensive anephric rats infused with 2 milliliters of a hyperosmolar solution of either sodium chloride or mannitol showed an increase in arterial pressure that was very pronounced with the sodium chloride and that could be partly abolished by administration of an antagonist to the vasopressor action of antidiuretic hormone (ADH). Rats with congenital ADH deficiency subjected to the same treatment showed smaller increments in arterial pressure that remained unchanged after administration of the ADH antagonist. Expansion of intravascular fluid volume was similar in all four groups and bore no correlation to the change in arterial pressure. It is concluded that about half of the increase in blood pressure induced by saline was attributable to the vasopressor effect of stimulated ADH and the remainder to an additional sodium-related factor, since it was more pronounced in the saline-infused than in the mannitol-infused groups. Expansion of the intravascular volume per se could only account for a minimal part of the increment in pressure.

Topics: Animals; Blood Pressure; Blood Volume; Disease Models, Animal; Hypertension; Male; Nephrectomy; Rats; Sodium; Vasoconstriction; Vasopressins

Topics: Animals; Desoxycorticosterone; Electrolytes; Hypertension; Hypertension, Malignant; Male; Plasma Volume; Rats; Sodium Chloride; Vasoconstrictor Agents; Vasopressins; Water

The action of prostacyclin (PGI2) on arterial pressure, heart rate, plasma concentration of angiotensin II and vasopressin was studied in groups of normal, renal hypertensive and DOC hypertensive rats. PGI2 was given by continuous iv. infusion at successive doses of 0.25, 0.5 and 1.0 microgram/kg x min, each rate for one hour. Arterial pressure was reduced to normal or below normal in the hypertensive rats, though the fall of blood pressure was greatest in the DOC hypertensive animals. Mean arterial pressure at the end of infusion was 89 mm Hg for normal rats, 87 mm Hg for renal hypertensive rats and 69 mm Hg for DOC hypertensive rats. Diastolic pressure fell more than systolic pressure suggesting a vasodilator mechanism. Heart rate was reduced significantly at the end of the infusion in the three groups of rats. Prostacyclin was also infused for 3 hours at a constant rate of 0.5 microgram/kg x min. The arterial pressure lowering effect was maintained throughout the infusion period.

Topics: Angiotensin II; Animals; Blood Pressure; Dose-Response Relationship, Drug; Epoprostenol; Half-Life; Heart Rate; Hypertension; Male; Prostaglandins; Rats; Vasopressins

Topics: Adolescent; Adult; Aged; Blood Pressure; Female; Humans; Hypertension; Male; Middle Aged; Vasopressins

In order to investigate the vasopressor role of ADH in the regulation of blood pressure, passive immunization experiments with an antibody to AVP were carried out in experimentally hypertensive rats. In hypertensive rats treated with deoxycorticosterone acetate (DOCA), spontaneously hypertensive rats (SHR) and spontaneously hypertensive stroke-prone rats (SHR-sp), the intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood pressure of 11 approximately 25mmHg, while in rats with two-kidney Goldblatt hypertension and normal rats, the blood pressure was not affected. This strongly suggests that ADH contributed to systemic vaso-constriction in DOCA hypertension and spontaneous hypertension in rats.

Topics: Animals; Blood Pressure; Cerebrovascular Disorders; Desoxycorticosterone; Hypertension; Hypothalamus; Immune Sera; Male; Pituitary Gland; Rats; Vasopressins

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA). 2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar-Kyoto (WK) rats; dose-response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds. 3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater. 4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats. 5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.

Topics: Angiotensin II; Animals; Blood Pressure; Hydroxydopamines; Hypertension; Kidney; Male; Norepinephrine; Rats; Serotonin; Sympathetic Nervous System; Vascular Resistance; Vasopressins

Topics: Animals; Body Fluid Compartments; Calcium; Catecholamines; Dogs; Humans; Hypertension; Kidney; Sodium Chloride; Vasopressins

Topics: Animals; Antigen-Antibody Reactions; Blood Pressure; Body Weight; Hematocrit; Hypertension; Hypertension, Malignant; Rats; Vasopressins; Water-Electrolyte Balance

A laboratory model was developed in the dog to quantitate the effects of cerebral venous hypertension on inappropriate antidiuretic hormone (ADH) secretion. When cerebral venous pressure was abruptly increased during continuous water loading, there was a sharp rise in urine osmolality within 30 minutes. Urine osmolality continued to increase during, and ten minutes after, the period of hypertension. On lowering cerebral venous pressure, the osmolality returned to baseline within 60 minutes. The effects could be extended for at least three hours and presumably longer. A 50% response threshold for this ADH effect occurred at a cerebral venous pressure between 18 and 19 cm of water. The effect correlated with plasma ADH levels. The study paralled documented clinical observations. The results are discussed in light of the recognition and management of surgical states where increased cerebral venous pressure might produce a severe antidiuretic effect.

Topics: Animals; Arginine Vasopressin; Brain; Cerebrovascular Disorders; Disease Models, Animal; Dogs; Hypertension; Hypothalamus; Osmolar Concentration; Time Factors; Vasopressins; Venous Pressure

A 60-year-old woman who had been instructed to increase her water intake because of nephrolithiasis developed the syndrome of inappropriate secretion of antidiuretic hormone when treated with chlorthalidone for mild hypertension. Serum osmolality was 235 mOsm/kg with concomitant urine osmolality of 490 mOsm/kg. When serum sodium decreased to 110 mEq/liter, plasma antidiuretic hormone (ADH) was elevated at 30 pg/ml. The syndrome resolved when chlorthalidone was discontinued together with fluid intake restriction. Plasma ADH returned to normal (less than 0.5 pg/ml) after three days of treatment. The favorable outcome in this patient is attributed to early recognition of the syndrome, which might occur even with nonthiazide diuretics such as chlorthalidone.

Topics: Chlorthalidone; Female; Humans; Hypertension; Kidney Calculi; Osmolar Concentration; Sodium; Time Factors; Vasopressins

A central stimulatory effect of angiotensin II (AII) on the secretion of arginine-vasopressin (AVP) has been described. The competitive blocker of AII, saralasin (SAR) has been used for diagnostic purposes in angiotensin-dependent hypertension. In addition SAR has a partially agnoistic effect. The aim of the present study was to demonstrate whether AVP-levels can be influenced during SAR-induced renin stimulation. In 9 patients with essential hypertension blood pressure dropped significantly under SAR (10 microgram/kg/min over a 30 min period). Before and after SAR plasma renin activity (PRA) and AVP were measured by RIA, SAR evoked significantly increments of PRA in all patients and of AVP in 6 patients. The increased serum concentrations of AVP following SAR may be explained either by the depressor effect of SAR, its diminished concentration at the central receptor, or a partial AII-agonistic effect.

Topics: Adolescent; Adult; Angiotensin II; Arginine Vasopressin; Female; Humans; Hypertension; Male; Middle Aged; Renin; Saralasin; Stimulation, Chemical; Vasopressins

Because vasopressin is one of the most potent naturally occurring pressor agents, and because of its importance in the regulation of blood volume and composition, we have undertaken a study of the role of vasopressin in the pathogenesis of the hypertension in the Okamoto-Aoki spontaneously hypertension (SH) rat. In SH rats, systolic blood pressure increased from 135 +/- 3 (SE) mmHg at age 33 days to 184 +/- 3 mmHg at age 75 days (P less than 0.01). In the Wistar-Kyoto (WKY) control rats, blood pressure increased from 100 +/- 2 to 120 +/- 2 mmHg (P less than 0.01). The differences in blood pressure between the SH and WKY rats at all ages were significant (P less than 0.01). During the age period 33-75 days, the 24-h urinary excretion of vasopressin in the SH rat was consistently more than twofold greater (P less than 0.01) than in the WKY rat. Plasma vasopressin concentration and pituitary vasopressin content were also elevated in the SH rat (P less than 0.01 and P less than 0.02, respectively). Changes in systolic blood pressure in the SH rat, however, were not paralleled by changes in the urinary excretion of vasopressin. The data indicate that the secretion of vasopressin is elevated in the SH rat. However, the magnitude of this elevation, in and of itself, may not be sufficient to account for the rising blood pressure in the young SH rat.

Topics: Animals; Body Weight; Hypertension; Male; Pituitary Gland, Posterior; Radioimmunoassay; Rats; Time Factors; Vasopressins

In order to test the integrity of central receptors, spontaneously hypertensive rats (SHR) of the Okamoto strain and weight-matched control rats of the Wistar Kyoto (WKY) strain were given intracerebroventricular (i.vt.) injections of carbachol and norepinephrine. The rats, in an unanesthetized, unrestrained state, were tested for drinking, antidiuretic and pressor responses. Antidiuretic hormone release was determined by using water loaded, diuresing rats as their own antidiuretic hormone bioassay. Blood pressure was measured directly from a femoral artery catheter. Drinking responses to i.vt. carbachol and antidiuretic responses to i.vt. carbachol and norepinephrine infusions were not different between SHR and WKY while pressor responses were potentiated in SHR. The potentiated pressor responses to central carbachol and norepinephrine injections were the result of increased vascular responsiveness to the antidiuretic hormone released by these drugs. A second, neurally mediated, factor was also apparent to i.vt. carbachol injections. This additional factor could be increased sympathetic outflow to central drug stimulation, increased vascular reactivity to sympathetic outflow, decreased baroreflex responses or a combination of the above.

Topics: Animals; Carbachol; Central Nervous System; Hexamethonium Compounds; Hypertension; Male; Norepinephrine; Phentolamine; Pressoreceptors; Rats; Vasomotor System; Vasopressins

Pressor reactivity to noradrenaline or vasopressin was studied in unanaesthetized, pithed and isolated perfused hindquarter, preparations from renal and spontaneously hypertensive rats. Unanaesthetized renal and spontaneously hypertensive rats showed hyperreactivity to noradrenaline and vasopressin. Vascular responses of noradrenaline in pithed and isolated perfused hindquarter preparations were to a lesser extent but significantly greater in the renal hypertensive rat, while responses of pithed and isolated perfused hindquarter preparations to noradrenaline were within normal limits in the spontaneously hypertensive rat.

Topics: Adrenalectomy; Animals; Hemodynamics; Hindlimb; Hydroxydopamines; Hypertension; Hypertension, Renal; Male; Norepinephrine; Rats; Sympathetic Nervous System; Vasopressins

Studies on the vasopressor role of the antidiuretic hormone arginine-vasopressin (AVP) in DOC hypertension, in two-kidney Goldblatt hypertension, and in spontaneous hypertension of rats, and during acute blood pressure elevation after intracerebroventricular injection of angiotensin II and in glycerol-induced acute renal failure of rats are reviewed. For the measurement of plasma AVP a radioimmunoassay has been developed. For this assay, a series of criteria has been met which allows the conclusion that, in plasma of rats, the antibody measures AVP only. For the blockade of vasopressor effects of AVP a specific antiserum has been used. On the basis of a series of control studies it has been concluded, but not proven that the antiserum lowers blood pressure exclusively by blockade of AVP. It could be shown that in the various animal models of hypertension and of acute blood pressure elevation AVP exerts systemic vasoconstriction when its plasma concentrations are elevated. In those models where the renin-angiotensin system played no role in blood pressure control, the height of blood pressure was closely related to the plasma AVP concentrations. When this relationship was compared with that obtained after the i.v. infusion or injection of AVP, a marked shift to the left became apparent. Hence, sensitization to the vasopressor effect of AVP had occurred, the factor of sensitization amounting to more than 1,000. It is concluded that AVP is not only an antidiuretic hormone but also a vasopressor hormone, and that any systemic vasopressor effect of AVP requires a mechanism of sensitization.

Topics: Acute Kidney Injury; Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Hypertension; Hypertension, Renal; Immune Sera; Injections, Intraventricular; Radioimmunoassay; Rats; Vasopressins

Because propranolol is contraindicated in some patients and since clonidine can decrease heart rate and renin release, clonidine was substituted for propranolol in 14 severely hypertensive minoxidil-treated outpatients. Clonidine induced weight loss which, since plasma concentrations were not suppressed, was not due to inhibition of release of antidiuretic hormone or renin. These endocrine interrelations were confirmed by later administration of clonidine to 4 of the subjects under controlled circumstances in our General Clinical Research Center. When substituted for propranolol, clonidine controlled blood pressure and heart rate in 8 of the 9 outpatients whose blood pressure had been previously well controlled. Clonidine and propranolol had additive antihypertensive effects in the other 5 patients. Thus, clonidine can substitute for propranolol or when added to the propranolol-vasodilator combination supply an additional blood pressure-lowering effects. This substitution or addition results in an increase in side effects. In addition, clonidine has a diuretic action under these circumstances by an unknown mechanism.

Topics: Adrenergic beta-Antagonists; Adult; Aldosterone; Blood Pressure; Clonidine; Drug Interactions; Female; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Minoxidil; Propranolol; Renin; Vasodilator Agents; Vasopressins

The concept of the "inappropriate" has a well-defined and easily comprehended meaning when applied to tumour secretion of antidiuretic hormone (A.D.H., vasopressin). When applied to high A.D.H. in other situations such as nephrotic syndrome, congestive cardiac failure, or cirrhosis, the use of the term "inappropriate secretion" simply reflects the fact that an easily measured controlling factor (plasma tonicity) is being overridden by a less easily measured one (effective extracellular volume). Similarly, sodium excretion in hypertension is said to be inappropriately low for the raised renal perfusion pressure: in this case inappropriateness results from the antinatriuretic effect of a minor degree of sodium depletion produced by pressure natriuresis. A similar objection can be made to the application of the term to the relations between renin or angiotensin-II concentrations and blood-pressure in some forms of hypertension. Since inappropriateness merely reflects the position and predilections of the observer, the widespread use of the term should be abandoned.

Topics: Angiotensin II; Animals; Blood Pressure; Diet; Diet, Sodium-Restricted; Humans; Hypertension; Hypertension, Renal; Kidney; Kidney Diseases; Models, Biological; Natriuresis; Paraneoplastic Endocrine Syndromes; Rats; Renin; Research; Sodium; Terminology as Topic; Vasopressins

Autopsy in a patient with severe hyponatremia showed central pontine myelinolysis. Review of our patients with central pontine myelinolysis and those described in the English literature to data disclosed that 61 percent had documented hyponatremia. While the exact mechanism involving hyponatremia and central pontine myelinolysis cannot be defined, a circumstantial relationship is apparent. The purpose of this paper is to emphasize this relationship and to suggest that the possibility of central pontine myelinolysis be considered in any patient with hyponatremia and neurologic dysfunction.

Topics: Alcoholism; Demyelinating Diseases; Diuretics; Fatty Liver; Female; Humans; Hypertension; Hyponatremia; Liver Function Tests; Middle Aged; Pons; Sodium; Vasopressins

The blood antidiuretic activity was studied in patients with hypertensive disease in a period between crises and during a hypertensive crisis. The antidiuretic activity of blood was found to be higher in patients who had crises than in those with no history of crises. Blood antidiuretic activity diminishes during a hypertensive crisis, which is evidently due to the inhibiting effect on the hypothalamus of the receptors of the cardiovascular system. Similar results were obtained in experiments in elevation of arterial pressure induced by electric stimulation of the hypothalamic nuclei. It is concluded that the antidiuretic hormone plays a pathogenetic role in hypertensive disease which is marked by the development of crises.

Topics: Adult; Animals; Electric Stimulation; Humans; Hypertension; Hypothalamus; Middle Aged; Rabbits; Vasopressins

Vasopressin (antidiuretic hormone, ADH), release in response to hemorrhage was studied in spontaneously hypertensive rats (SHR), Kyoto-Wistar rats (KWR), and Wistar rats (WR). The rats were anesthetized with pentobarbital sodium and ADH concentration was measured before and after three successive hemorrhages at 15 min intervals. The blood samples for radioimmunoassay (RIA) of ADH were collected from the external jugular vein. The ADH release in response to hemorrhage was significantly reduced in debuffered WR (carotid and aortic baroceptors and atrioventricular receptors deafferented), intact KWR and intact SHR when compared to the intact WR.

Topics: Animals; Chemoreceptor Cells; Hemorrhage; Hypertension; Male; Pressoreceptors; Rats; Vasopressins

During the onset of malignant hypertension (MH) in rats treated with deoxycorticosterone trimethylacetate (DOC), plasma arginine vasopressin (AVP) concentrations increase tenfold as a consequence of hypovolemia and hyperosmolality. In benign hypertensive (BH) rats, plasma AVP is increased threefold in comparison with control animals. Plasma renin is markedly suppressed in both BH and MH animals. In MH rats, biologically active AVP antiserum lowers blood pressure (BP) transiently to normal or subnormal levels; in BH rats, a small BP-lowering effect of the AVP antiserum is seen. (Biologically active angiotensin II antiserum does not lower BP in MH rats.) The relationship between the height of BP and plasma AVP concentration in DOC hypertensive rats indicates, when compared with that relationship in diabetes insipidus rats infused with AVP, a marked enhancement of the vasopressor effect of AVP. These findings and the earlier observation of vasopressin-induced vascular damage by Byrom (F. B. Byrom, The Hypertensive Vascular Crisis. London: Heinemann, 1969) strongly suggest that ADH is involved as a vasopressor hormone in the pathogenesis of malignant DOC hypertension.

Topics: Angiotensin II; Animals; Antibodies; Arginine Vasopressin; Blood Pressure; Body Weight; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Hypertension, Malignant; Immune Sera; Male; Nephrectomy; Osmolar Concentration; Rats; Renin; Sodium; Urea; Vasomotor System; Vasopressins

The brain isorenin angiotensin system has been implicated in the development of spontaneous hypertension by several investigators. The experiments reported here were designed to test the responsiveness of unanesthetized spontaneous hypertensive (SH) rats to intracerebroventricular angiotensin II injections compared to Wistar-Kyoto (WK) normotensive controls. The results indicate that there is no difference between SH and WK animals in drinking responses or antidiuretic hormone release to central angiotensin II injections; however, an increased pressor responsiveness to intraventricular angiotensin II in SH as compared to WK was observed. The results of intravenous infusions of pressor substances in these experiments and reports by other investigators suggest that the increased blood pressure effects to central angiotensin are due to three possible factors: 1) increased vascular responsiveness of SH to vasoconstrictor substances in general, 2) increased vascular sensitivity of SH rats to sympathetic outflow, and 3) decreased baroreceptor reflexes to acute increases in blood pressure. We suggest that the brain isorenin-angiotensin system may be involved in spontaneous hypertension by increased production of angiotensin II or by activation of a potentiated sympathetic system, but not by a generalized increased sensitivity of brain receptors to central angiotensin.

Topics: Angiotensin II; Animals; Blood Pressure; Diuresis; Dose-Response Relationship, Drug; Drinking; Heart Rate; Hypertension; Injections, Intravenous; Injections, Intraventricular; Male; Rats; Vasopressins

Topics: Adolescent; Adult; Chromium; Diuresis; Female; Glomerulonephritis; Humans; Hypertension; Kidney; Kidney Diseases; Kidney Function Tests; Male; Mannitol; Middle Aged; Nephrotic Syndrome; Pyelonephritis; Vasopressins

Topics: Adrenal Glands; Blood Pressure; Cardiac Output; Catecholamines; Diabetes Insipidus; Humans; Hypertension; Kidney; Renin; Sleep; Smoking; Stress, Psychological; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction; Vasopressins

Topics: Adenoma; Adrenal Cortex Neoplasms; Animals; Humans; Hypertension; Hypertension, Malignant; Rats; Vasopressins

The threshold of serum osmolality causing release of vasopressin (antidiuretic hormone) was shifted to an abnormally low level (262 mosmol/kg H2O) in a 14-year-old girl with hypertension and signs of hypoplastic corpus callosum. There was a physiologically meaningful control of vasopressin release in response to water restriction and water load. Plasma vasopressin concentrations (range 1.2--11.9 pg/ml) were of the same magnitude as those of healthy adults, being abnormally high only when related to the hypotonicity of serum observed. Plasma concentrations of angiotensin II were higher than expected from the suppressed levels of plasma renin activity. Blood-pressure response to angiotensin II infusion was increased. Resetting of the osmostat and hypertension may both be explained by lesions of the central nervous system.

Topics: Adolescent; Agenesis of Corpus Callosum; Aldosterone; Angiotensin II; Arginine Vasopressin; Blood Pressure; Female; Humans; Hypertension; Osmolar Concentration; Renin; Sodium Chloride; Syndrome; Vasopressins; Water-Electrolyte Balance

Plasma concentrations of arginine-vasopressin (antidiuretic hormone) have been measured in 40 patients with benign essential hypertension and 12 patients with malignant-phase hypertension. Values tended to be low in the benign phase and high in the malignant phase. 5 normal subjects were infused with synthetic arginine-vasopressin, producing plasma concentrations up to five times the highest value recorded in malignant-phase hypertension, without any effect on blood-pressure. There is no evidence that vasopressin has a direct role in the pathogenesis of benign essential hypertension or its transition to the malignant phase. On the contrary, abnormal vasopressin concentrations may be caused by hypertension.

Topics: Adult; Aged; Arginine Vasopressin; Blood Pressure; Female; Humans; Hypertension; Hypertension, Malignant; Infusions, Parenteral; Male; Middle Aged; Vasopressins

The paper analyses the results of a study of the clinical peculiarities of the course of essential hypertension with crises, of the changes in the functional state of the central nervous system, and of some neuro-humoral systems of the human body. In most of the patients tending to develope frequent crises distinct changes were noted in the EEG that indicate dysfunction of the hypothalamic zone and of the reticular formation of the brain stem, their clinical course being characterized by significant astheno-neurotic disorders with autonomous dysfunction and cerebral angiodistonic disturbances. For the prevention of crises it is essential to conduct a pathogenetically substantiated and highly differentiated systematic therapy, as well as special measures aimed at increasing the endurance of the central nervous system, improving the circulation and metabolic processes in the brain, decreasing tnd hypothalamic structures of the brain, and correcting the dishormonal disorders.

Topics: Adult; Antihypertensive Agents; Brain; Cerebral Arteries; Cerebrovascular Disorders; Diencephalon; Humans; Hypertension; Middle Aged; Physical Therapy Modalities; Reticular Formation; Vasopressins

Topics: Cerebrovascular Disorders; Humans; Hypertension; Hypothalamus; Pituitary Gland, Posterior; Vasopressins

Compared with a group of normal pregnant women, matched for age, parity, posture, and length of gestation, women with hypertension and proteinuria in the last trimester had significantly lower plasma concentrations of renin, renin substrate and angiotensin II. Plasma aldosterone and DOC concentrations were also lower in the hypertensive group. The plasma levels of cortisol, corticosterone, and ADH showed no significant difference. Plasma renin concentration was raised throughout normal pregnancy, and part of this increase appeared to be due to the presence of an inactive form of renin. Plasma concentrations of renin substrate, angiotensin II, and aldosterone were also raised in normal pregnant women, but concurrent measurement of these substances showed no significant relationship between them, renin, and plasma electrolytes in mid- or late gestation. A study of five women in the weeks immediately after conception showed increases in plasma angiotensin II and aldosterone concentrations, which were significantly related at this very early stage of pregnancy. Total 24-hour urinary sodium increased gradually from about two weeks after gestation to the end of the study five weeks later. This increase was due mainly to a rise in overnight sodium excretion, with a fall in the day/night ratio. No relationship was found between plasma angiotension II or aldosterone concentrations and day, night, or total 24 hour sodium excretion.

Topics: Adrenal Cortex Hormones; Aldosterone; Angiotensin II; Angiotensinogen; Arginine Vasopressin; Corticosterone; Desoxycorticosterone; Female; Humans; Hydrocortisone; Hypertension; Ovulation; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, First; Renin; Sodium; Vasopressins

Topics: Adult; Aged; Aging; Animals; Arrhythmias, Cardiac; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Humans; Hypertension; Middle Aged; Rabbits; Rats; Vasopressins

The demonstration that the components required for the generation of angiotensin II are present in the brain has led to the proposal that there is a brain renin-angiotensin system. To test this hypothesis, experiments were performed to determine if biologically active amounts of angiotensin II are formed when renin is injected into the cerebral ventricles. The effects of central administration of agents known to block the peripheral renin-angiotensin system were also investigated. It was shown that intraventricular renin increased water intake, blood pressure and ADH secretion and that these effects were blocked by saralasin. These findings indicated an interaction between injected renin, brain angiotensinogen and converting enzyme, resulting in the formation of angiotensin II in physiologically active concentrations. However, these experiments did not demonstrate a role for endogenous brain renin activity. Central administration of saralasin in normal animals did not decrease water intake, blood pressure or ADH secretion. These studies thus failed to demonstrate a physiological role for the proposed brain renin-angiotensin system in controlling water balance and blood pressure.

Topics: Angiotensin II; Angiotensinogen; Animals; Blood Pressure; Brain; Dogs; Drinking; Hypertension; Rats; Renin; Saralasin; Swine; Vasopressins

Topics: Bronchial Neoplasms; Humans; Hypertension; Radioimmunoassay; Vasopressins

Topics: Aldosterone; Angiotensin II; Animals; Blood Pressure; Dogs; Feedback; Hypertension; Kidney; Potassium; Sodium; Vasopressins

1. The rate of renal excretion of arginine-vasopressin was determined during unrestricted fluid intake for 24 h and in response to fluid deprivation for 18 h in nine young men with very mild essential hypertension and compared with that in sixteen normotensive men of similar age. 2. Despite an equivalent osmolar stimulus, excretion of arginine-vasopressin was significantly greater in the reference group than in the reference group. This difference increased progressively with increasing dehydration. 3. We suggest that these findings are mainly due to an increased rate of secretion of arginine-vasopressin in response to mild hydropenia in hypertensive patients and that a moderate increase of release of arginine-vasopressin during periods of fluid deprivation may exert vascular effects and thus influence the perpetuation of hypertension.

Topics: Adult; Arginine Vasopressin; Dehydration; Humans; Hypertension; Male; Osmolar Concentration; Vasopressins

Topics: Aged; Body Weight; Diuretics; Humans; Hypertension; Hyponatremia; Polythiazide; Potassium; Potassium Chloride; Potassium Deficiency; Sodium; Vasopressins; Water-Electrolyte Balance

During the past decade the diagnostic use of blood volume determinations has declined as a result of the generation of largely inaccurate results and inappropriate normalization and interpretation. After historical development of more than 50 years, current methodology employs 125I-labeled human serum albumin and 51Cr-labeled red blood cells to determine plasma volume and red cell volume, respectively. Accurate blood volume determinations require (1) abandoning the use of the mean body hematocrit:venous hematocrit ratio and using simultaneous independent measurements of both volumes; (2) delaying multiple postinjection patient samples until complete mixing and equilibration are complete; (3) backextrapolation of plasma concentrations of 125I to account for albumin loss from the plasma, and, rarely, back-extrapolation of red cell concentrations to account for dilution by red cells transfused during the procedure; (4) normalization of volumes by adjusting patient weight to normal correspondence with lean tissue mass, whenever necessary. A rapid, routine method that fulfills these four requirements is presented. A number of surgical and medical conditions in which blood volume determinations are very useful in diagnosis and therapy are discussed. Recently developed techniques for blood volume measurements include neutron acativation analysis and fluorescent excitation analysis. Correct normalization of accurate blood volume measurements will provide a valuable service to the entire medical community.

Topics: Aged; Blood Volume Determination; Body Constitution; Carbon Monoxide; Central Venous Pressure; Chromium Radioisotopes; Diagnostic Errors; Erythrocytes; Hematocrit; Hormones, Ectopic; Humans; Hyperaldosteronism; Hypertension; Indium; Iron Radioisotopes; Male; Phosphorus Radioisotopes; Plasma Volume; Polycythemia; Postoperative Complications; Potassium Radioisotopes; Radioisotope Dilution Technique; Serum Albumin, Radio-Iodinated; Shock; Technetium; Time Factors; Transferrin; Vasopressins

Topics: Angiotensin II; Arm; Arteries; Autonomic Nervous System; Blood Pressure; Blood Viscosity; Blood Volume; Brain; Cardiac Output; Cardiovascular Physiological Phenomena; Cerebrovascular Circulation; Epinephrine; Female; Humans; Hypertension; Kidney; Leg; Liver Circulation; Norepinephrine; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Regional Blood Flow; Uterus; Vascular Resistance; Vasopressins

Topics: Adult; Animals; Diuresis; Female; Heart Failure; Humans; Hypertension; Liver Cirrhosis; Male; Rats; Vasopressins; Water-Electrolyte Balance

Topics: Humans; Hypertension; Vasopressins

Topics: Arginine; Diabetes Insipidus; Humans; Hypertension; Hyponatremia; Radioimmunoassay; Vasopressins

Topics: Adult; Aldosterone; Blood Pressure; Blood Vessels; Catecholamines; Female; Humans; Hydrocortisone; Hypertension; Male; Norepinephrine; Obesity; Pulse; Vasopressins

Topics: Animals; Aorta, Thoracic; Barium; Blood Pressure; Blood Vessels; Body Weight; Chlorides; Dose-Response Relationship, Drug; Female; Heart Rate; Heart Ventricles; Hemodynamics; Hypertension; Hypertension, Renal; Kidney; Male; Muscle, Smooth; Norepinephrine; Organ Size; Rats; Regional Blood Flow; Stimulation, Chemical; Vascular Resistance; Vasopressins

Topics: Animals; Blood Pressure; Blood Vessels; Capillary Resistance; Hemodynamics; Hypertension; Norepinephrine; Papaverine; Rats; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Topics: Animals; Aorta, Abdominal; Blood Pressure; Constriction; Depression, Chemical; Female; Hindlimb; Hypertension; Ligation; Muscle Contraction; Muscle, Smooth; Norepinephrine; Rats; Regional Blood Flow; Time Factors; Vascular Resistance; Vasopressins

Topics: Aged; Creatinine; Desoxycorticosterone; Diuresis; Edema; Heart Failure; Humans; Hypertension; Infusions, Parenteral; Male; Middle Aged; Osmolar Concentration; Prostatic Hyperplasia; Prostatic Neoplasms; Prostatitis; Sodium; Time Factors; Urea; Urinary Catheterization; Urination Disorders; Vasopressins; Water-Electrolyte Balance

Topics: Adrenal Glands; Animals; Blood Pressure; Body Weight; Desoxycorticosterone; Electrophoresis, Disc; Female; Ganglia, Autonomic; Hypertension; Myocardium; Norepinephrine; Organ Size; Pentolinium Tartrate; Pituitary Gland; Rats; Rats, Inbred Strains; Sound; Spleen; Thymus Gland; Time Factors; Tyramine; Vasopressins

Topics: Adrenal Glands; Angiotensin II; Animals; Body Weight; Female; Hippocampus; Hypertension; Kidney; Noise; Norepinephrine; Organ Size; Pituitary Gland; Rats; Rats, Inbred Strains; Septal Nuclei; Septum Pellucidum; Thyroid Gland; Tyramine; Vasopressins

Topics: Animals; Blood Gas Analysis; Blood Pressure; Cardiac Output; Coronary Circulation; Dogs; Drug Combinations; Esophageal and Gastric Varices; Heart Rate; Hemodynamics; Hemorrhage; Hepatic Artery; Hypertension; Injections, Intravenous; Isoproterenol; Liver Circulation; Portal Vein; Time Factors; Vasopressins

Topics: Ammonia; Angiotensin II; Animals; Bilirubin; Blood Glucose; Blood Pressure; Blood Proteins; Blood Urea Nitrogen; Cholesterol; Dogs; Hypertension; Liver Function Tests; Norepinephrine; Portacaval Shunt, Surgical; Transaminases; Vasopressins

Topics: Adrenal Glands; Aldosterone; Ascites; Blood Pressure; Calcium; Creatinine; Cyclic AMP; Edema; Glomerular Filtration Rate; Humans; Hydrocortisone; Hypertension; Kidney; Kidney Failure, Chronic; Kidney Tubules; Liver Cirrhosis; Magnesium; Osmolar Concentration; Phosphates; Potassium; Prostaglandins; Renin; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Anesthesia, Intravenous; Aneurysm; Angiography; Angiotensin II; Animals; Arteriovenous Fistula; Blood Pressure Determination; Dye Dilution Technique; Hypertension; Ischemia; Kidney; Norepinephrine; Phentolamine; Punctures; Rabbits; Spectrophotometry; Thrombosis; Trimethaphan; Urinary Catheterization; Vasopressins

Topics: Eclampsia; Female; Headache; Humans; Hypertension; Methylergonovine; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Syndrome; Vasopressins

Topics: Acne Vulgaris; Adrenal Cortex Hormones; Adrenalectomy; Androgens; Androstanols; Breast Neoplasms; Estrogens; Female; Hirsutism; Hormones; Humans; Hypercalcemia; Hypertension; Hypophysectomy; Male; Nandrolone; Norethindrone; Ovarian Neoplasms; Progesterone; Prostatic Neoplasms; Thyroid Hormones; Thyroid Neoplasms; Urogenital Neoplasms; Uterine Neoplasms; Vasopressins

Topics: Acetylcholine; Animals; Blood Pressure Determination; Cardiac Output; Decamethonium Compounds; Dogs; Drug Antagonism; Drug Synergism; Hypertension; Methods; Nicotine; Pituitary Gland, Posterior; Pituitary Hormones; Tissue Extracts; Tolazoline; Vascular Resistance; Vasopressins; Yohimbine

1. The responses of the mean arterial pressure to (-)-noradrenaline, tyramine, angiotensin II-val(5)-amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone.2. Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals.3. Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade.4. Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade.5. Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension.6. Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension.

Topics: Anesthesia, General; Angiotensin II; Animals; Arteries; Autonomic Nerve Block; Blood Pressure; Desoxycorticosterone; Diuretics; Furosemide; Hydrochlorothiazide; Hypertension; Hypertension, Renal; Male; Norepinephrine; Pentobarbital; Rats; Renin; Sodium Chloride; Tyramine; Vasoconstrictor Agents; Vasopressins

Topics: Angiotensin II; Animals; Aorta, Thoracic; Culture Techniques; Desoxycorticosterone; Disease Models, Animal; Hypertension; Hypertension, Renal; Male; Norepinephrine; Phenylephrine; Rabbits; Rats; Renin; Tyramine; Vasoconstrictor Agents; Vasopressins

Topics: Adrenocorticotropic Hormone; Arginine; Chromatography, Paper; Humans; Hydrocortisone; Hypertension; Hypoglycemia; Oxidoreductases; Vasopressins

Topics: Antihypertensive Agents; Blood Pressure; Common Cold; Humans; Hypertension; Phenylephrine; Vasopressins

Topics: Adult; Chlorides; Diagnosis, Differential; Epilepsy; Female; Humans; Hypertension; Hyponatremia; Porphyrias; Porphyrins; Pregnancy; Puerperal Disorders; Vasopressins

Topics: Animals; Desoxycorticosterone; Hypertension; In Vitro Techniques; Nephrectomy; Norepinephrine; Perfusion; Sodium Chloride; Tail; Vascular Resistance; Vasopressins

Topics: Animals; Blood Pressure; Body Weight; Desoxycorticosterone; Heart; Hypertension; In Vitro Techniques; Male; Nephrectomy; Norepinephrine; Perfusion; Potassium; Rats; Sodium Chloride; Tail; Vascular Diseases; Vascular Resistance; Vasopressins

Topics: Adult; Biological Transport; Depression, Chemical; Diuretics; Female; Furosemide; Humans; Hypertension; Hypertonic Solutions; Kidney; Kidney Concentrating Ability; Lysine; Male; Middle Aged; Sodium; Sodium Chloride; Urine; Vasopressins; Water

Topics: Humans; Hypertension; Hypogonadism; Hypothyroidism; Myxedema; Thyroid Function Tests; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Catecholamines; Corticotropin-Releasing Hormone; Epinephrine; Histamine; Hypertension; Hypothalamus; Injections; Norepinephrine; Oxytocin; Pituitary Gland; Pituitary Hormones, Posterior; Rats; Serotonin; Vasopressins

Topics: Adult; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypophysectomy; Insulin; Male; Testosterone; Vasopressins

Topics: Adult; Aged; Aldosterone; Arteriosclerosis; Blood Pressure; Blood Volume; Cardiac Output; Chronic Disease; Digitalis Glycosides; Diuretics; Electrocardiography; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Kidney; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Regional Blood Flow; Serum Albumin, Radio-Iodinated; Vasopressins

Topics: Adult; Aged; Cobalt Isotopes; Diuresis; Diuretics; Female; Glomerular Filtration Rate; Humans; Hypertension; Hypertension, Renal; Iodine Isotopes; Iodohippuric Acid; Kidney Function Tests; Male; Mannitol; Middle Aged; Pyelonephritis; Renal Artery Obstruction; Urea; Vasopressins; Vitamin B 12

Topics: Animals; Coronary Vessels; Dipyridamole; Electrocardiography; Heart; Heart Ventricles; Hypertension; Ischemia; Myocardium; Norepinephrine; Perfusion; Propranolol; Radioisotopes; Rubidium; Vasopressins

Topics: Angiotensin II; Animals; Dogs; Hypertension; Injections, Subcutaneous; Kidney; Nephrectomy; Rats; Renin; Species Specificity; Tissue Extracts; Vasopressins

Topics: Animals; Blood Pressure; Desoxycorticosterone; Diabetes Insipidus; Homeostasis; Hydrocortisone; Hypertension; Hypothalamo-Hypophyseal System; Male; Pituitary Gland, Posterior; Rats; Stereotaxic Techniques; Vasopressins; Water-Electrolyte Balance

Topics: Angiotensin II; Animals; Hexamethonium Compounds; Hypertension; Hypertension, Renal; Male; Norepinephrine; Rats; Vasopressins

Topics: Angiotensin II; Blood Pressure; Diagnosis, Differential; Humans; Hypertension; Hypertension, Renal; Renal Artery Obstruction; Vasopressins

Topics: Angiotensin II; Animals; Atropine; Blood Pressure; Ergotamine; Female; Heart; Hypernatremia; Hypertension; Injections, Intravenous; Male; Oxytocin; Peptides; Rats; Sodium Chloride; Vagotomy; Vasopressins

Topics: Acetazolamide; Adolescent; Adult; Aged; Aging; Aminophylline; Calcium; Chlorothiazide; Glomerulonephritis; Humans; Hypertension; Male; Mannitol; Middle Aged; Organomercury Compounds; Pyelonephritis; Vasopressins

Topics: Animals; Diet; Genetics; Hypertension; Hypertonic Solutions; Natriuresis; Rats; Sodium Chloride; Vasopressins

Topics: Blood Pressure Determination; Diagnosis; Diuresis; Glomerular Filtration Rate; Humans; Hypertension; Hypertension, Renal; Insulin; Kidney; Kidney Diseases; Kidney Function Tests; Natriuresis; Pharmacology; Renal Artery Obstruction; Urea; Vasopressins

Topics: Blood Transfusion; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Mortality; Omentum; Splenectomy; Surgical Procedures, Operative; Vasopressins

Topics: Angiotensins; Blood Circulation; Epinephrine; Humans; Hypertension; Kidney; Norepinephrine; Pharmacology; Renal Circulation; Vasopressins

Topics: Adrenocorticotropic Hormone; Blood Pressure; Cortisone; Endocrinology; Hypertension; Hypophysectomy; Luteinizing Hormone; Oxytocin; Pharmacology; Pituitary Gland; Pituitary Gland, Posterior; Propylthiouracil; Rats; Research; Testosterone; Thyrotropin; Thyroxine; Vasopressins

Topics: Angiotensins; Drug Therapy; Humans; Hypertension; Hypertension, Portal; Liver Diseases, Parasitic; Methysergide; Schistosomiasis; Selective Serotonin Reuptake Inhibitors; Serotonin; Vasopressins

Topics: Angiotensin II; Animals; Arteries; Hypertension; In Vitro Techniques; Norepinephrine; Perfusion; Rats; Solutions; Vasomotor System; Vasopressins

Topics: Aldosterone; Angiotensins; Animals; Blood Pressure; Corticosterone; Desoxycorticosterone; Female; Hypertension; Hypertension, Renal; Kidney; Norepinephrine; Pregnancy; Pregnancy, Animal; Rats; Renin; Research; Vasopressins

Topics: Adrenalectomy; Adrenocorticotropic Hormone; Aldosterone; Animals; Arginine Vasopressin; Cortisone; Desoxycorticosterone; Hypertension; Hypophysectomy; Physiology; Rats; Rats, Inbred SHR; Research; Thyroid Hormones; Thyroidectomy; Thyrotropin; Vasopressins

Topics: Alcoholism; Blood Pressure Determination; Blood Volume Determination; Heart Function Tests; Hepatic Veins; Humans; Hypertension; Hypertension, Portal; Iodine Isotopes; Liver Circulation; Liver Cirrhosis; Liver Function Tests; Oxytocin; Pharmacology; Pituitary Hormones, Posterior; Rose Bengal; Serum Albumin; Serum Albumin, Radio-Iodinated; Vasopressins

Topics: Arginine Vasopressin; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Hypertension; Lysine; Obesity; Vasopressins

Topics: Adolescent; Biomedical Research; Blood Pressure; Cardiac Catheterization; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Geriatrics; Humans; Hypertension; Hypertension, Portal; Infusions, Parenteral; Liver Circulation; Liver Cirrhosis; Lysine; Pharmacology; Phenylalanine; Portal Pressure; Portal Vein; Toxicology; Vasopressins

Topics: Angiotensins; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Pharmacology; Toxicology; Vasopressins

Topics: Angina Pectoris; Coronary Disease; Digoxin; Electrocardiography; Hydrochlorothiazide; Hypercholesterolemia; Hypertension; Metaraminol; Nitroglycerin; Shock; Shock, Cardiogenic; Vasopressins; Warfarin

Topics: Angiotensins; Blood Pressure; Blood Pressure Determination; Blood Vessels; Diet; Eating; Genetic Predisposition to Disease; Genetics; Hypertension; Norepinephrine; Pharmacology; Rats; Research; Sodium Chloride; Vasopressins

Topics: Adrenalectomy; Angiotensins; Arginine Vasopressin; Atropine; Ergotamine; Hypertension; Nephrectomy; Oxytocin; Pharmacology; Rats; Regeneration; Research; Vagotomy; Vasopressins

Topics: Blood Transfusion; Cryosurgery; Esophageal and Gastric Varices; Gastric Hypothermia; Hematemesis; Hypertension; Hypertension, Portal; Hypothermia, Induced; Liver Cirrhosis; Liver Diseases; Neomycin; Prognosis; Surgical Procedures, Operative; Vasopressins

Topics: Bis-Trimethylammonium Compounds; Epinephrine; Hypertension; Hypertension, Renal; Pharmacology; Rabbits; Renal Artery Obstruction; Research; Vasomotor System; Vasopressins

Topics: Blood Pressure; Body Weight; Diuresis; Edema; Female; Glomerulonephritis; Humans; Hypertension; Hypertension, Renal; Inulin; Kidney; Kidney Function Tests; Nephrosclerosis; Osmolar Concentration; Pathology; Pharmacology; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Vasopressins

Topics: Animals; Cats; Cerebral Ventricles; Diuresis; Hypertension; Lateral Ventricles; Oxytocin; Pituitary Hormones; Pituitary Hormones, Posterior; Vasopressins

Topics: Arginine Vasopressin; Atropine; Cardiovascular System; Chlorisondamine; Hemodynamics; Humans; Hypertension; Norepinephrine; Serotonin; Tetraethylammonium Compounds; Tyramine; Vasopressins

Topics: Atropine; Bradykinin; Caffeine; Chlorpromazine; Dibucaine; Ergot Alkaloids; Humans; Hypertension; Lysergic Acid Diethylamide; Morphine; Oxytocin; Peptides; Phenoxybenzamine; Reserpine; Tripelennamine; Vasopressins; Vitamin B 12

Topics: Blood Transfusion; Esophageal and Gastric Varices; Esophagoscopy; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Liver Function Tests; Pituitary Hormones, Posterior; Portography; Splenectomy; Surgical Procedures, Operative; Vasopressins; Vitamin K

Topics: Adrenocorticotropic Hormone; Aldosterone; Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Cortisone; Desoxycorticosterone; Hormones; Hypertension; Norepinephrine; Progesterone; Rats; Rats, Inbred SHR; Research; Sodium Chloride; Spironolactone; Stilbenes; Testosterone; Thyroid Hormones; Vasopressins

Topics: Adrenal Glands; Adrenalectomy; Blood; Catecholamines; Heart; Heart Function Tests; Hypertension; Pathology; Perfusion; Rats; Regeneration; Research; Vasopressins

Topics: Angiotensins; Arteriosclerosis; Hypertension; Hypertension, Renal; Kidney; Skin Tests; Vasopressins

Topics: Blood Circulation; Blood Pressure; Felypressin; Heart Function Tests; Hemodynamics; Hepatic Artery; Hepatic Veins; Humans; Hypertension; Hypertension, Portal; Liver Cirrhosis; Pharmacology; Vasopressins

Topics: Abdomen; Anemia; Angiotensins; Antihypertensive Agents; Blood Circulation; Bradykinin; Coronary Vessels; Ganglionic Blockers; Heart Diseases; Hypertension; Hyperthyroidism; Hypothyroidism; Liver Circulation; Niacin; Pharmacology; Polycythemia; Serotonin; Shock; Vasopressins; Xanthines

Topics: Adult; Arteriosclerosis; Ductus Arteriosus; Ductus Arteriosus, Patent; Familial Primary Pulmonary Hypertension; Humans; Hypertension; Hypertension, Pulmonary; Lung Diseases; Pathology; Pharmacology; Pulmonary Circulation; Rabbits; Research; Vasopressins

Topics: Arginine Vasopressin; Arteries; Electrolytes; Epinephrine; Humans; Hypertension; In Vitro Techniques; Norepinephrine; Potassium; Vasopressins

Topics: Acetylcholine; Adrenal Glands; Animals; Arginine Vasopressin; Epinephrine; Hypertension; Norepinephrine; Oxytocin; Rats; Regeneration; Vasopressins

Topics: Arginine Vasopressin; Body Fluids; Body Weight; Creatine; Creatinine; Hypertension; Natriuresis; Sodium; Urine; Vasopressins

Topics: Amine Oxidase (Copper-Containing); Arginine Vasopressin; Bradykinin; Guinea Pigs; Hypertension; Intestines; Neostigmine; Serotonin; Vasopressins

Topics: Aldosterone; Angiotensin Amide; Angiotensin II; Heart Defects, Congenital; Heart Failure; Humans; Hypertension; Kidney; Vasopressins

Topics: Arginine Vasopressin; Disease; Epinephrine; Hexamethonium; Hypertension; Rats; Rodent Diseases; Thiourea; Vasoconstrictor Agents; Vasopressins

Topics: Animals; Arginine Vasopressin; Desoxycorticosterone; Hypertension; Rats; Vasopressins

Topics: Essential Hypertension; Hypertension; Infusions, Parenteral; Kidney; Vasopressins

Topics: Arginine Vasopressin; Humans; Hypertension; Hypertension, Portal; Liver; Vasopressins

Topics: Arginine Vasopressin; Humans; Hypertension; Sodium; Sodium Chloride; Sodium Chloride, Dietary; Vasopressins; Water

Topics: Animals; Arginine Vasopressin; Hypertension; Rats; Sodium; Sodium, Dietary; Vasopressins

Topics: Arginine Vasopressin; Humans; Hypertension; Sodium; Vasopressins

Topics: Animals; Arginine Vasopressin; Hypertension; Kidney; Rats; Sodium; Sodium Chloride; Vasopressins; Water

Topics: Arginine Vasopressin; Hypertension; Sodium; Vasopressins

Topics: Animals; Arginine Vasopressin; Hypertension; Rats; Vasopressins

Topics: Animals; Hypertension; Hypertension, Renal; Rats; Vasopressins

Topics: Arginine Vasopressin; Humans; Hypertension; Vasopressins

Topics: Hormones; Hypertension; Pituitary Gland; Pituitary Gland, Posterior; Urine; Vasopressins

Topics: Arginine Vasopressin; Desoxycorticosterone; Desoxycorticosterone Acetate; Hypertension; Kidney; Vasopressins

Topics: Blood; Blood Pressure; Blood Pressure Determination; Diuresis; Diuretics; Hypertension; Vasopressins

Topics: Blood Pressure; Body Fluids; Diuresis; Diuretics; Hypertension; Urine; Vasopressins

Topics: Blood Pressure; Hypertension; Pituitary Diseases; Pituitary Gland; Pituitary Hormones; Vasopressins