pituitrin and Hypoxia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients. When symptomatic (hyponatremic encephalopathy), the overall morbidity is 34%. Individuals most susceptible to death or permanent brain damage are prepubescent children and menstruant women. Failure of the brain to adapt to the hyponatremia leads to brain damage. Major factors that can impair brain adaptation include hypoxia and peptide hormones. In children, physical factors--discrepancy between skull size and brain size--are important in the genesis of brain damage. In adults, certain hormones--estrogen and vasopressin (usually elevated in cases of hyponatremia)--have been shown to impair brain adaptation, decreasing both cerebral blood flow and oxygen utilization. Initially, hyponatremia leads to an influx of water into the brain, primarily through glial cells and largely via the water channel aquaporin (AQP)4. Water is thus shunted into astrocytes, which swell, largely preserving neuronal cell volume. The initial brain response to swelling is adaptation, utilizing the Na(+)-K(+)-ATPase system to extrude cellular Na(+). In menstruant women, estrogen + vasopressin inhibits the Na(+)-K(+)-ATPase system and decreases cerebral oxygen utilization, impairing brain adaptation. Cerebral edema compresses the respiratory centers and also forces blood out of the brain, both lowering arterial Po(2) and decreasing oxygen utilization. The hypoxemia further impairs brain adaptation. Hyponatremic encephalopathy leads to brain damage when brain adaptation is impaired and is a consequence of both cerebral hypoxia and peptide hormones.

Topics: Adaptation, Physiological; Age Factors; Blood-Brain Barrier; Brain; Brain Edema; Cell Size; Estrogens; Humans; Hyponatremia; Hypoxia; Organ Size; Sex Factors; Vasopressins

A survey is given on the regulation of the formation of corticoliberin and of pro-opiomelanocortin and of ACTH, respectively, and on the significance of these compounds. The formation of pro-opiomelanocortin is furthered by corticoliberin, vasopressin, oxytocin and angiotensin II. Receptors for the binding of corticoliberin appear in numerous parts of the central nervous system. In various diseases the content of corticoliberin in the plasma and in certain tissues is changed. The inhibition of the ACTH secretion by glucocorticosteroids takes place via a decrease of the formation of corticoliberin and by a reduction of the equipment of the corticotrophic cells with receptors for its binding. The secretion of corticoliberin and of ACTH, respectively, is increased by loads, by hypoglycaemia, by blood losses, by hypoxia and by infections. In the glucocorticosteroid receptors there are 2 types with different affinity to cortisol and corticosterone.

Topics: Adrenocorticotropic Hormone; Angiotensin II; Corticotropin-Releasing Hormone; Hemorrhage; Humans; Hypoglycemia; Hypoxia; Infections; Oxytocin; Pro-Opiomelanocortin; Receptors, Cell Surface; Vasopressins

A number of naturally occurring substances can evoke endothelium-dependent responses in isolated blood vessels. In most arteries studied, acetylcholine, adenosine diphosphate (ADP), adenosine triphosphate (ATP), arachidonic acid, bradykinin, and thrombin cause endothelium-dependent relaxations. In veins, however, the endothelium-dependent inhibitory effect of acetylcholine, ATP, and thrombin often is transient and/or modest, as it is masked by the direct stimulating action of these substances on the venous smooth muscle; arachidonic acid evokes endothelium-dependent augmentation of the contractile response to norepinephrine. Aggregating platelets cause an endothelium-dependent relaxation of certain but not all arteries and veins that is probably mediated by released serotonin and ADP. The endothelium of the coronary artery may enhance the relaxations caused by catecholamines. Vasopressin causes endothelium-dependent relaxations in cerebral and coronary arteries but not in systemic blood vessels. Hypoxia causes endothelium-dependent increases in tension in systemic arteries and in pulmonary arteries and veins but not in limb veins. The heterogeneity in endothelium-dependent responsiveness may reflect variations in sensitivity of either endothelial or vascular smooth-muscle cells of different anatomical origin.

Topics: Acetylcholine; Adenosine Diphosphate; Animals; Arachidonic Acid; Arachidonic Acids; Blood Vessels; Bradykinin; Catecholamines; Endothelium; Humans; Hypoxia; In Vitro Techniques; Platelet Aggregation; Serotonin; Thrombin; Vasopressins

Topics: Adrenocorticotropic Hormone; Adult; Alkalosis, Respiratory; Anaphylaxis; Animals; Cardiovascular Diseases; Collagen Diseases; Gastrointestinal Diseases; Gonadotropins; Hematologic Diseases; Hormones, Ectopic; Humans; Hypoxia; In Vitro Techniques; Infant, Newborn; Lung; Lung Diseases; Lung Neoplasms; Microscopy, Electron; Neuromuscular Diseases; Neurotransmitter Agents; Paraneoplastic Endocrine Syndromes; Pulmonary Edema; Pulmonary Embolism; Pulmonary Emphysema; Rats; Respiratory Distress Syndrome, Newborn; Skin Diseases; Syndrome; Vasopressins

Topics: Anesthesia; Anesthesia, Epidural; Anesthesia, General; Anesthesia, Spinal; Anesthetics; Angiotensin II; Animals; Anuria; Glomerular Filtration Rate; Hemodynamics; Humans; Hypotension; Hypoxia; Kidney; Kidney Function Tests; Preanesthetic Medication; Regional Blood Flow; Renin; Shock, Hemorrhagic; Vasopressins; Water-Electrolyte Balance

Topics: Budd-Chiari Syndrome; Chemical and Drug Induced Liver Injury; Collateral Circulation; Epinephrine; Hepatic Artery; Humans; Hypertension, Portal; Hypoxia; Liver Circulation; Liver Cirrhosis; Liver Diseases; Norepinephrine; Portal System; Vasopressins; Venous Pressure

Topics: Acetates; Adrenocorticotropic Hormone; Amino Acids; Animals; Butyrates; Carbohydrates; Catecholamines; Cats; Cattle; Cricetinae; Dinitrophenols; Dogs; Ducks; Female; Glucagon; Glucose; Growth Hormone; Hormones; Humans; Hypoglycemic Agents; Hypoxia; In Vitro Techniques; Insulin; Insulin Secretion; Oxytocin; Pancreas; Pregnancy; Propionates; Rabbits; Rats; Sheep; Swine; Sympatholytics; Thyroid Hormones; Vasopressins

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

A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC.. Four weeks after MCT 60 mg kg. PHC was associated with increased RV dilatation and paradoxical septal motion. Vasopressin increased MBP [mean (standard error)] from 52.6 (3.8) to 125.0 (8.9) mm Hg and CI from 25.4 (2.3) to 40.6 (1.8) ml min. In this rat model of a PHC, vasopressin, but not phenylephrine or norepinephrine, resulted in better haemodynamic and vascular recovery.

Topics: Acute Disease; Animals; Drug Evaluation, Preclinical; Echocardiography; Hemodynamics; Hypertension, Pulmonary; Hypoxia; Male; Monocrotaline; Nordefrin; Oxygen; Partial Pressure; Phenylephrine; Rats, Sprague-Dawley; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Inflammatory bowel disease (IBD) is a chronic intestinal disorder, often leading to an impaired quality of life in affected patients. The importance of environmental factors in the pathogenesis of IBD, including their disease-modifying potential, is increasingly recognised. Hypoxia seems to be an important driver of inflammation, as has been reported by our group and others. The aim of the study is to evaluate if hypoxia can alter disease activity of IBD measured by Harvey-Bradshaw Activity Index in Crohn's disease (increase to ≥5 points) and the partial Mayo Score for ulcerative colitis (increase to ≥2 points). To test the effects of hypoxia under standardised conditions, we designed a prospective and controlled investigation in healthy controls and patients with IBD in stable remission.. This is a prospective, controlled and observational study. Participants undergo a 3-hour exposure to hypoxic conditions simulating an altitude of 4000 metres above sea level (m.a.s.l.) in a hypobaric pressure chamber. Clinical parameters, as well as blood and stool samples and biopsies from the sigmoid colon are collected at subsequent time points.. The study protocol was approved by the Ethics Committee of the Kanton Zurich (reference KEK-ZH-number 2013-0284). The results will be published in a peer-reviewed journal and shared with the worldwide medical community.. NCT02849821; Pre-results.

Topics: Adolescent; Adult; Altitude; Angiotensins; Biopsy; Blood Pressure; Colitis, Ulcerative; Colon, Sigmoid; Crohn Disease; Cytokines; Feces; Healthy Volunteers; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Leukocyte L1 Antigen Complex; Middle Aged; Organ Size; Prospective Studies; Research Design; Severity of Illness Index; Sigmoidoscopy; Urinary Bladder; Vasopressins; Young Adult

Cardiovascular dysfunction in asphyxiated neonates contributes significantly to their morbidity and mortality. We have recently shown that a low-dose vasopressin infusion (0.005 - 0.01 units/kg per hour) may improve myocardial oxygen transport balance in a swine model of neonatal hypoxia-reoxygenation. We aimed to compare the systemic and regional hemodynamic effects of low-dose vasopressin to dobutamine, a synthetic beta-adrenoreceptor agonist. Piglets (1 - 5 days old, 1.6 - 2.2 kg) were anesthetized and instrumented to continuously monitor systemic hemodynamic parameters, including cardiac output and mesenteric flow indices. After 2 h of hypoxia (10% - 15% O2), piglets had normoxic reoxygenation for 4 h. In a blinded randomized fashion, piglets received infusion of either vasopressin (0.01 units/kg per hour started at 30 min of reoxygenation) or dobutamine (20 μg/kg per minute started at 2 h of reoxygenation) (n = 8 per group). Hypoxia-reoxygenation controls (placebo, n = 8) and sham-operated (n = 5) piglets were also studied. Tissue lactate, glutathione, glutathione disulfide, and lipid hydroperoxides levels and histology of the left ventricle and the small bowel were analyzed. Plasma was also analyzed for troponin-I and intestinal fatty acid-binding protein levels. Piglets subjected to hypoxia-reoxygenation had cardiogenic shock and metabolic acidosis, which improved on reoxygenation. During recovery, cardiac output and mesenteric flows gradually deteriorated and were increased similarly in vasopressin- and dobutamine-treated piglets (P < 0.05 vs. controls). Plasma troponin-I and left ventricular lactate levels were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls), with no difference in the histological analysis among groups. The intestinal GSSG/GSH ratio and lipid hydroperoxides level were lower in the vasopressin and dobutamine groups (P < 0.05 vs. controls). This study is the first to demonstrate that a low-dose vasopressin infusion used in the setting of neonatal swine model of hypoxia-reoxygenation is associated with an improvement in cardiac output and mesenteric perfusion.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Cardiac Output; Dobutamine; Glutathione; Heart Ventricles; Hypoxia; Lactic Acid; Lipid Peroxides; Mesenteric Artery, Superior; Oxygen; Reperfusion Injury; Shock, Cardiogenic; Swine; Troponin I; Vasopressins

In the present study, we aimed to elucidate the effects of chronic vasopressin administration on renal medullary oxygen levels.. Adult Sprague Dawley or vasopressin-deficient Brattleboro rats were treated with the vasopressin V2 receptor agonist, desmopressin (5 ng/h; 3d), or its vehicle via osmotic minipumps. Immunostaining for pimonidazole and the transcription factor HIF-1α (hypoxia-inducible factor-1α) were used to identify hypoxic areas. Activation of HIF-target gene expression following desmopressin treatment was studied by microarray analysis.. Pimonidazole staining was detected in the outer and inner medulla of desmopressin-treated rats, whereas staining in control animals was weak or absent. HIF-1α immunostaining demonstrated nuclear accumulation in the papilla of desmopressin-treated animals, whereas no staining was observed in the controls. Gene expression analysis revealed significant enrichment of HIF-target genes in the group of desmopressin-regulated gene products (P = 2.6*10(-21) ). Regulated products included insulin-like growth factor binding proteins 1 and 3, angiopoietin 2, fibronectin, cathepsin D, hexokinase 2 and cyclooxygenase 2.. Our results demonstrate that an activation of the renal urine concentrating mechanism by desmopressin causes renal medullary hypoxia and an upregulation of hypoxia-inducible gene expression.

Topics: Animals; Deamino Arginine Vasopressin; Disease Models, Animal; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney Medulla; Nitroimidazoles; Oxygen; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Receptors, Vasopressin; Signal Transduction; 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

Chronic intermittent hypoxia (CIH) is a concomitant of sleep apnea that produces a slowly developing chemosensory-dependent blood pressure elevation ascribed in part to NMDA receptor-dependent plasticity and reduced nitric oxide (NO) signaling in the carotid body. The hypothalamic paraventricular nucleus (PVN) is responsive to hypoxic stress and also contains neurons that express NMDA receptors and neuronal nitric oxide synthase (nNOS). We tested the hypothesis that extended (35 d) CIH results in a decrease in the surface/synaptic availability of the essential NMDA NR1 subunit in nNOS-containing neurons and NMDA-induced NO production in the PVN of mice. As compared with controls, the 35 d CIH-exposed mice showed a significant increase in blood pressure and an increased density of NR1 immunogold particles located in the cytoplasm of nNOS-containing dendrites. Neither of these between-group differences was seen after 14 d, even though there was already a reduction in the NR1 plasmalemmal density at this time point. Patch-clamp recording of PVN neurons in slices showed a significant reduction in NMDA currents after either 14 or 35 d exposure to CIH compared with sham controls. In contrast, NO production, as measured by the NO-sensitive fluorescent dye 4-amino-5-methylamino-2',7'-difluorofluorescein, was suppressed only in the 35 d CIH group. We conclude that CIH produces a reduction in the surface/synaptic targeting of NR1 in nNOS neurons and decreases NMDA receptor-mediated currents in the PVN before the emergence of hypertension, the development of which may be enabled by suppression of NO signaling in this brain region.

Topics: Analysis of Variance; Animals; Arginine; Blood Gas Analysis; Blood Pressure; Cyclic N-Oxides; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Free Radical Scavengers; Hydrogen-Ion Concentration; Hypoxia; Imidazoles; In Vitro Techniques; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; N-Methylaspartate; Neuronal Plasticity; Neurons; Nitric Oxide; Nitric Oxide Synthase Type I; Paraventricular Hypothalamic Nucleus; Receptors, N-Methyl-D-Aspartate; S-Nitroso-N-Acetylpenicillamine; Signal Transduction; Time Factors; Vasopressins

The purpose of this study was to determine whether the increased expression of tyrosine hydroxylase (TH), the first and limiting enzyme in catecholamine synthesis in vasopressin (VP) neurons of the human neonate, represents a primary developmental phenomenon or reflects a secondary phenomenon related to the activation of VP systems due to perinatal hypoxia. Using immunohistochemistry, we investigated TH expression in the supraoptic nucleus (SON) of 15 human neonates at autopsy in relation to the age and severity/duration of hypoxic injury that was estimated on the basis of neuropathological criteria. Increased expression of TH was observed selectively in VP-synthesizing neurons of neonates who experienced prolonged perinatal hypoxia; was not related to the age, body weight/percentile, brain weight, or head perimeter of the subjects but depended on the neuropathological grade of the hypoxic injury (p < 0.01); and was found in VP-synthesizing neurons with increased cellular and nuclear size, that is, neurons with histological evidence of activation. Taken together, these observations indicate that increased expression of TH in VP neurons of SON is not developmentally determined but represents a response to hypoxic stress. We propose that increased TH expression in SON neurons of the human neonate may serve as a neuropathological marker of prolonged perinatal hypoxia in autopsy material.

Topics: Autopsy; Female; Gene Expression Regulation, Developmental; Humans; Hypoxia; Immunophilins; Infant; Male; Neurons; Oxytocin; Severity of Illness Index; Statistics as Topic; Supraoptic Nucleus; Tyrosine 3-Monooxygenase; Vasopressins

Hypoxic stimulation of the carotid body receptors (CBR) results in a rapid hyperglycemia with an increase in brain glucose retention. Previous work indicates that neurohypophysectomy inhibits this hyperglycemic response. Here, we show that systemic arginine vasopressin (AVP) induced a transient, but significant, increase in blood glucose levels and increased brain glucose retention, a response similar to that observed after CBR stimulation. Comparable results were obtained after intracerebral infusion of AVP. Systemic AVP-induced changes were maintained in hypophysectomized rats but were not observed after adrenalectomy. Glycemic changes after CBR stimulation were inhibited by pharmacological blockage of AVP V1a receptors with a V1a-selective receptor antagonist ([beta-Mercapto-beta,beta-cyclopentamethylenepropionyl1,O-me-Tyr2, Arg8]-vasopressin). Importantly, local application of micro-doses of this antagonist to the liver was sufficient to abolish the hyperglycemic response after CBR stimulation. These results suggest that AVP is a mediator of the hyperglycemic reflex and cerebral glucose retention following CBR stimulation. We propose that hepatic activation of AVP V1a receptors is essential for this hyperglycemic response.

Topics: Adrenal Glands; Adrenalectomy; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Brain Chemistry; Carotid Body; Catecholamines; Chemoreceptor Cells; Enzyme Inhibitors; Glucagon; Glucose; Hyperglycemia; Hypoxia; Liver; Male; Rats; Rats, Wistar; Receptors, Vasopressin; Sodium Cyanide; Vasopressins

Twin fetuses experience much higher rates of perinatal mortality/morbidity than age- and weight-matched singletons. Across species, the prepartum increase in fetal plasma cortisol is responsible for maturing a number of systems in preparation for birth and the immediate postnatal period. In sheep, it is known that basal adrenocortical function is delayed in twins relative to singletons. Thus, it could be argued that relative immaturity in twins may explain their increased susceptibility to stress in the perinatal period and their relatively poor perinatal outcome. However, whether adrenocortical responsiveness to stress is also diminished in the twin fetus and whether the fetal cardiovascular, metabolic and endocrine defences to acute stress are comparatively weak in the twin fetus is unknown. This study investigated the effect of twinning on adrenocortical responsiveness to either the physiological stress of acute hypoxaemia or to an exogenous ACTH test, and on the fetal cardiovascular, metabolic and endocrine responses to acute hypoxaemic stress. Twenty Welsh Mountain sheep fetuses were chronically instrumented (1-2% halothane) at 121 +/- 3 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit-time flow probe around a femoral artery. The animals were divided into two groups based upon fetal number (singletons, n= 10; twins, n= 10), as determined at surgery. At 130 +/- 2 days, a 1 h episode of acute, isocapnic hypoxaemia (to reduce carotid P(O(2)) to 12 +/- 1 mmHg) was induced in all fetuses by reducing the maternal inspired O(2) fraction (F(IO(2)); 9% O(2) in N(2)). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. At 133 +/- 2 days a 2.5 microg bolus dose of synthetic ACTH (Synacthen; Ciba Pharmaceuticals, UK) was injected i.v. into eight of the singleton and six of the twin fetuses to determine adrenocortical steroidogenic sensitivity to exogenous ACTH. Under basal conditions, twins had lower plasma cortisol concentration, arterial blood pressure and femoral blood flow relative to singleton fetuses. Twins responded to acute hypoxaemia with similar pressor and vasopressor responses compared to singleton fetuses. However, the rate pressure product, an index of myocardial work, tended to decr

Topics: Acid-Base Equilibrium; Adrenal Cortex; Adrenocorticotropic Hormone; Animals; Blood Gas Analysis; Body Weight; Catecholamines; Endocrine Glands; Female; Fetus; Hormones; Hydrocortisone; Hypoxia; Organ Size; Pregnancy; Sheep; Stress, Physiological; Twins; Vasopressins

This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is approximately 145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 +/- 1 dGA, half of the fetuses (n = 13) were continuously infused I.V. with dexamethasone for 48 h at a rate of 2.06 +/- 0.13 microg kg-1 h-1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 +/- 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 +/- 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin responses were enhanced, whilst the prolonged bradycardia and augmented plasma NPY responses persisted. These data show that fetal treatment with dexamethasone modifies the pattern and magnitude of fetal cardiovascular responses to acute oxygen deprivation. Modifications to different mechanisms mediating the fetal defence responses to acute hypoxaemia that occur during dexamethasone treatment may reverse, persist or even become enhanced by 48 h following the treatment period.

Topics: Acid-Base Equilibrium; Acute Disease; Animals; Blood Pressure; Carbon Dioxide; Catecholamines; Chemoreceptor Cells; Dexamethasone; Endocrine System; Female; Fetus; Glucocorticoids; Heart Rate, Fetal; Hypoxia; Neuropeptide Y; Oxygen; Pregnancy; Regional Blood Flow; Sheep; Vascular Resistance; Vasopressins

The vasopressin gene is expressed in the suprachiasmatic nucleus where the basic helix-loop-helix (bHLH)-PAS factors CLOCK and MOP3 regulate circadian expression through interactions with E-box sequences. We have examined vasopressin gene regulation by HIF-1alpha, a bHLH-PAS factor involved in responses to hypoxia. By transfecting Neuro-2A cells with 5' flanking regions of vasopressin gene driving a luciferase reporter, we have shown that CLOCK and HIF-1alpha cooperate in the induction of expression from 1000 bp and 350 bp of the vasopressin promoter but do not activate a 120-bp promoter fragment. The region between -191 and -128 contains an E-box A that appears to be essential for HIF-1alpha/CLOCK-mediated transcriptional activity. However, gel-shift analysis shows that the cooperative effect of HIF-1alpha and CLOCK results in MOP3 binding, but does not involve heterodimerization of HIF-1alpha/CLOCK, at E-box A. These data indicate that cross-talk between mediators of hypoxic and circadian pathways can regulate target genes.

Topics: 5' Flanking Region; Animals; ARNTL Transcription Factors; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Circadian Rhythm; CLOCK Proteins; Dimerization; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Molecular Sequence Data; Neuroblastoma; Promoter Regions, Genetic; Protein Structure, Tertiary; Trans-Activators; Transcription Factors; Transcriptional Activation; Tumor Cells, Cultured; Vasopressins

Although it is established that the fetus can successfully withstand a single, acute hypoxaemic challenge during gestation, little is known about what effects prevailing adverse intrauterine conditions might have on the fetal response to acute hypoxaemia. The aims of this study were therefore: (1) to characterise the effects of prevailing and sustained hypoxaemia, acidaemia or hypoglycaemia on the fetal cardiovascular responses to an episode of acute hypoxaemia; and (2) to determine the effects of these adverse intrauterine conditions on mechanisms mediating these cardiovascular responses. Thirty-three Welsh Mountain sheep fetuses were chronically instrumented (1-2 % halothane) between 117 and 125 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit-time flow probe around a femoral artery. The animals were divided retrospectively into four groups based upon post-surgical, sustained, basal blood oxygen (chronically hypoxaemic; P(a,O2), 17.3 +/- 0.5 mmHg; n = 8), glucose (chronically hypoglycaemic; blood glucose, 0.49 +/- 0.03 mmol l(-1); n = 6) and acid-base (chronically acidaemic; pH(a), 7.25 +/- 0.01; n = 5) status. Values for compromised fetuses were -2 S.D. from a group of control (n = 14) fetuses. At 130 +/- 4 days, a 1 h episode of acute, isocapnic hypoxaemia (9 % O(2) in N(2), to reduce carotid P(a,O2) to 12 +/- 1 mmHg) was induced in all fetuses by reducing the maternal inspired O(2) fraction (F(I,O2)). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. During acute hypoxaemia all fetuses elicited hypertension, bradycardia and femoral vasoconstriction. However, prevailing fetal compromise altered the cardiovascular and endocrine responses to a further episode of acute hypoxaemia, including: (1) enhanced pressor and femoral vasoconstriction; (2) greater increments in plasma noradrenaline and vasopressin during hypoxaemia; and (3) basal upward resetting of hypothalamic-pituitary-adrenal axis function. Only chronically hypoxaemic fetuses had significantly elevated basal concentrations of noradrenaline and enhanced chemoreflex function during acute hypoxaemia. These data show that prevailing adverse intrauterine conditions alter the capacity of the fetus to respond to a subsequent episode o

Topics: Acid-Base Equilibrium; Acidosis; Acute Disease; Adrenocorticotropic Hormone; Animals; Blood Gas Analysis; Blood Glucose; Cardiovascular System; Catecholamines; Chemoreceptor Cells; Endocrine System; Female; Fetal Diseases; Fetus; Hemoglobins; Hindlimb; Hydrocortisone; Hydrogen-Ion Concentration; Hypoglycemia; Hypoxia; Lactic Acid; Pregnancy; Sheep; Vascular Resistance; Vasopressins

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

It was previously observed that infusion of angiotensin II, hypertonic saline and N-methyl-D-aspartic acid (NMDA) causes an increase in vasopressin and cardiodepressant factor release from the posterior pituitary lobe into the blood (Goraca 1998). The aim of present study was to investigate if the cardiodepressant factor and vasopressin are simultaneously released from the pituitary into the blood dialysate during acute hypoxia.. The samples of dialysates of venous blood outflowing from the vicinity of cavernous sinus of the sella turcica were collected in anaesthetized rats. 30-min hypoxia was obtained by increasing the respiratory dead space. The concentration of vasopressin in blood dialysate was determined by radioimmunoassay, and cardiodepressant activity on spontaneously discharging pacemaker tissue of the right auricle of the right heart atrium.. Acute hypoxia caused simultaneously an increase in cardiodepressant activity and vasopressin concentration in the blood dialysate outflowing from the vicinity of cavernous sinus of the sella turcica.. These data suggest that cardiodepressant factor released together with vasopressin from the posterior pituitary lobe decrease the heart contraction rate and improves coronary circulation affected by vasopressin release.

Topics: Animals; Bicarbonates; Carbon Dioxide; Dialysis; Female; Hydrogen-Ion Concentration; Hypoxia; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Depressant Factor; Oxygen; Rats; Rats, Wistar; Sella Turcica; Vasopressins; Veins

1. The effects of fetal intravenous treatment with phentolamine or a vasopressinergic V1-receptor antagonist on the fetal cardiovascular responses to acute hypoxaemia in the llama were investigated. 2. Six llama fetuses were surgically prepared between 60 and 70 % of gestation under general halothane anaesthesia with vascular catheters and transit-time ultrasonic flow probes around a carotid artery and a femoral artery. At least 4 days after surgery all fetuses were subjected to a 3 h experiment: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery while on slow i.v. infusion with saline. On separate days this experiment was repeated with fetal i.v. treatment with either phentolamine or a V1-receptor antagonist dissolved in saline. 3. During saline infusion all llama fetuses responded to acute hypoxaemia with intense femoral vasoconstriction. Phentolamine during normoxia produced hypotension, tachycardia and vasodilatation in both the carotid and the femoral circulations. During hypoxaemia, fetuses treated with phentolamine did not elicit the pronounced femoral vasoconstriction and all died within 20 min of the onset of hypoxaemia. A V1-receptor antagonist produced a femoral vasodilatation during normoxia but did not affect the fetal cardiovascular responses to acute hypoxaemia. 4. In conclusion, alpha-adrenergic and V1-vasopressinergic mechanisms contribute to a basal vasoconstrictor tone in the femoral circulation in the llama fetus. The enhanced femoral vasoconstriction during acute hypoxaemia in the llama fetus is not mediated by stimulation of V1-vasopressin receptors, but is dependent on alpha-adrenergic receptor stimulation. Such alpha-adrenergic efferent mechanisms are indispensable to fetal survival during hypoxaemia in the llama since their abolition leads to cardiovascular collapse and death.

Topics: Adrenergic alpha-Antagonists; Algorithms; Animals; Antidiuretic Hormone Receptor Antagonists; Blood Gas Analysis; Camelids, New World; Carotid Arteries; Female; Femoral Artery; Fetus; Hemodynamics; Hypoxia; Phentolamine; Pregnancy; Sympathetic Nervous System; Vasodilation; Vasopressins

It is well known that altitude natives differ from sea level natives in aspects of fluid and electrolyte homeostasis.. To evaluate exercise and environmental influences on the electrolyte and water status in hypoxia adapted subjects, we investigated 11 well-trained marathon runners (33.7 +/- 0.7 yr, 60.5 +/- 1.9 kg), native to an altitude above 2600 m, before and after two marathon races. One competition was held at moderate altitude (AM, 2650 m, 14 degrees C, 55% RH, running time 3 h 6 min +/- 22 min) and another under tropical conditions (HM, 470 m, 28 degrees C, 70% RH, running time 2 h 54 min +/- 30 min). Blood samples were taken 3 d before, immediately after, 1 h after, and 24 h after the races.. The loss in body fluid was calculated to be 2.15 L during AM and 5.05 L during HM, respectively. It was compensated mostly by ingested fluids without electrolyte content and by metabolically produced water, which led to hyponatremia during AM (plasma [Na+] from 144.3 +/- 0.7 to 131.7 +/- 2.1 mmol x L(-1)). Severe dehydration without significant changes in plasma [Na+] could be detected after HM. Serum antidiuretic hormone concentrations and serum aldosterone concentrations significantly increased during both races and remained at a high level for at least 1h after both competitions. Serum atrial natriuretic peptide (ANP) concentrations were at a high level at rest, increasing during HM, and decreasing during AM.. Under tropical conditions, we found a severe state of dehydration characterized by an extended ANP-response, which was not prevented by water intake during the race. Under hypoxic conditions, however, we found that hyponatremia had developed. This can be partly explained by pure water intake and metabolically produced water, and also, possibly, by a special hypoxia-induced effect.

Topics: Adult; Aldosterone; Altitude; Dehydration; Electrolytes; Humans; Hypernatremia; Hypoxia; Male; Running; Vasopressins

Because pial artery dilation during a 20- or 40-min hypoxic exposure was less than that observed during a 5- or 10-min exposure, stimulus duration determines the vascular response to hypoxia. Dynorphin (Dyn) modulates hypoxic pial dilation and contributes to decremented dilation during longer hypoxic exposures. This study was designed to determine whether vasopressin (VP) contributes to Dyn modulation of hypoxic pial dilation in newborn pigs equipped with a closed cranial window. Moderate (M) and severe (S) hypoxia (arterial PO2 approximately 35 and 25 mmHg, respectively) had no effect on cerebrospinal fluid VP during a 5-min exposure but increased its concentration during longer exposure periods. The VP antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,O-Me-Tyr2, Arg8]vasopressin (MEAVP) had no influence on pial dilation during the 5-min exposure but potentiated the 20- and 40-min M and S hypoxic exposure dilations: 21 +/- 2 vs. 29 +/- 3% and 23 +/- 2 vs. 33 +/- 2% for 20- and 40-min S hypoxic dilation before and after MEAVP. Topical VP during 5 min of hypoxia elicited dilation that was reversed to vasoconstriction during 20 min of S and 40 min of M and S hypoxia. Similarly, during 5 min of hypoxia, Dyn elicited dilation that was reversed to vasoconstriction during longer hypoxic periods. MEAVP blunted this Dyn-induced vasoconstriction. These data show that VP modulates hypoxic pial dilation in a stimulus duration-dependent manner and that VP contributes to the reversal of Dyn from a dilator to a constrictor during prolonged hypoxia. Finally, these data suggest that VP contributes to Dyn modulation of hypoxic cerebrovasodilation.

Topics: Animals; Arginine Vasopressin; Arteries; Blood Pressure; Cerebrovascular Circulation; Drug Synergism; Dynorphins; Female; Gases; Hormone Antagonists; Hydrogen-Ion Concentration; Hypoxia; Male; Pia Mater; Swine; Time Factors; Vasodilation; Vasopressins

The mechanism causing peripheral oedema in hypoxaemic chronic obstructive pulmonary disease has not been established. Vasopressin, a powerful antidiuretic hormone involved in salt and water homeostasis, is released in response to acute hypoxia. However, the effect of prolonged hypoxaemia on hypothalamic and pituitary release of the magnocellular hypothalamic hormones, vasopressin and oxytocin, has not previously been studied.. Male Wistar rats were randomly allocated to either normobaric, hypoxic (10% O2) or control (21% O2) environmental chambers. An initial series of experiments examined plasma vasopressin concentration, osmolality, sodium concentration, packed cell volume (PCV), and weight gain at weekly intervals (n = 4-6) for six weeks. The maximum increase in plasma vasopressin concentration and PCV occurred after five weeks. In a second experiment vasopressin and oxytocin concentrations in the hypothalamus, pituitary gland, and plasma were measured in eight control and eight hypoxic rats after five weeks in the environmental chambers.. In rats exposed to environmental hypoxia PCV increased (p < 0.001) and weight gain decreased (p < 0.05) compared with controls. The plasma vasopressin concentration increased progressively from a baseline of 1.36 (0.2) pmol/l (n = 6) to a maximum of 4.38 (0.8) pmol/l (n = 6; p < 0.01) during the first five weeks of environmental hypoxia (difference 3.02 (95% CI 1.18 to 4.86)). Plasma osmolality and sodium concentration were unchanged in hypoxic rats compared with controls during the six week period. The hypothalamic vasopressin concentration was increased (p < 0.001) after five weeks of environmental hypoxia (91.6 (4.8) pmol/ hypothalamus) compared with controls (57.4 (5.1) pmol/hypothalamus), the difference being 34.2 pmol/hypothalamus (95% CI 21.6 to 46.5). The pituitary vasopressin concentration was unchanged. In hypoxic rats hypothalamic oxytocin (59.6 (3.2) pmol/hypothalamus) was greater (p < 0.01) than in controls (42 (3.8) pmol/hypothalamus), a difference of 17.6 pmol/ hypothalamus (95% CI 8.7 to 26.5). Similarly, the plasma oxytocin concentration was increased (p < 0.05) in hypoxic rats (6.78 (1.2) pmol/l) compared with controls (3.3 (0.8) pmol/l), a difference of 3.48 pmol/l (95% CI 0.89 to 6.07). The pituitary oxytocin concentration was unchanged in the two groups.. These results demonstrate an increase in hypothalamic production of vasopressin and oxytocin in rats during prolonged hypoxaemia. Increased plasma concentrations of neurohypophysial hormones would be expected to impair sodium and water homeostasis in patients with hypoxaemia. However, the absence of change in the plasma osmolality and sodium concentrations in this study and previous clinical investigations suggests that compensatory mechanisms modulate the actions of both vasopressin and oxytocin. A reduction in renal blood flow or decreased renal responsiveness to the neurohypophyseal hormones may be involved.

Topics: Animals; Hematocrit; Hypothalamus; Hypoxia; Male; Osmolar Concentration; Oxygen; Oxytocin; Pituitary Gland; Random Allocation; Rats; Rats, Wistar; Sodium; Vasopressins; Weight Gain

It has been observed that a vasopressin receptor antagonist attenuates hypoxic hyperemia in fetal sheep, whereas methionine enkephalin (Met) and leucine enkephalin (Leu) contribute to hypoxia-induced pial artery dilation in newborn pigs. This study was designed to investigate the relationship between vasopressin and opioids in hypoxia-induced pial artery dilation in the newborn pig by use of the closed cranial window technique. Hypoxia-induced pial artery dilation was attenuated during moderate [arterial Po2 (PaO2) approximately 35 mmHg] and severe hypoxia (PaO2 approximately 25 mmHg) by the vasopressin receptor antagonist, [beta-mercapto-beta beta-cyclopentamethylenepropionyl, 2-O-Me-Tyr2, Arg8]vasopressin (MeAVP, 5 micrograms/kg i.v.; 29 +/- 1 vs. 14 +/- 2 and 37 +/- 2 vs. 18 +/- 2% for moderate and severe hypoxia in absence vs. presence of MeAVP, respectively, n = 7). Hypoxia-induced dilation was accompanied by increased cerebrospinal fluid (CSF) vasopressin concentration (26 +/- 1 vs. 67 +/- 4 and 26 +/- 1 vs. 99 +/- 4 pg/ml for control vs. moderate and control vs. severe hypoxia, n = 5). Vasopressin increased CSF Met (895 +/- 28, 1,147 +/- 63, 1,327 +/- 48, and 1,600 +/- 75 pg/ml for control and 40, 400, and 4,000 pg/ml vasopressin, respectively, n = 7). CSF Leu concentration was similarly increased by vasopressin. Furthermore, MeAVP attenuated the release of Met during moderate hypoxia (910 +/- 38 and 2,682 +/- 49 vs. 911 +/- 38 and 2,110 +/- 84 pg/ml for control and moderate hypoxia in absence and presence of MeAVP, respectively, n = 5). MeAVP had similar effects on hypoxia-induced Leu release. These data show that vasopressin contributes to hypoxia-induced pial artery dilation and that vasopressin increases CSF Met and Leu concentrations. These data also suggest that elevated CSF vasopressin concentrations that occur during hypoxemia result in opioid release, which subsequently contributes to hypoxic pial artery dilation.

Topics: Animals; Arginine Vasopressin; Cerebral Arteries; Chromatography, High Pressure Liquid; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Female; Hormone Antagonists; Hypoxia; Male; Osmolar Concentration; Pia Mater; Radioimmunoassay; Vasodilation; Vasopressins

Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop sodium and water retention and a subclinical autonomic neuropathy. The possibility that these might be associated has been investigated.. The ability of 24 patients with COPD to excrete a 6 ml/kg 2.7% intravenous saline or 15 ml/kg oral water load was studied and changes in plasma electrolyte levels, osmolality, plasma aldosterone and vasopressin levels, urinary volume and sodium content, glomerular filtration rate, renal blood flow, and cardiovascular autonomic nerve function were measured. Patients were divided into groups of eight: those in group A (controls) had mild COPD with a Pa02 of > 9 kPa and no oedema, patients in group B were more hypoxaemic but had never been oedematous, whilst those in group C were hypoxaemic and mildly oedematous at the time of the study.. Patients in groups B and C excreted less sodium and water during saline loading and a lesser proportion of the water load. Patients in group C had a reduction in renal blood flow and glomerular filtration rate and all had a subclinical autonomic neuropathy, which was also found in three patients in group B. Their plasma aldosterone level was raised but did suppress appropriately on saline loading. Vasopressin levels were abnormally raised for the osmolality in patients in group C and in those with autonomic dysfunction throughout the water load and at 240 minutes after the salt load. Sodium and urine excretion was highly correlated with autonomic dysfunction, aldosterone levels at time zero, and renal blood flow. The 11 patients with autonomic dysfunction were more likely to be oedematous, more hypoxaemic, excreted much less urine and sodium, had lower glomerular filtration rate and renal blood flow, and higher aldosterone and vasopressin levels than the remaining patients.. In patients with COPD the inability to excrete sodium and water is multifactorial. This is the first study to show that autonomic dysfunction is at least associated and might play an important part in the impaired sodium and water homeostasis seen in patients with severe COPD.

Topics: Aged; Aldosterone; Autonomic Nervous System Diseases; Glomerular Filtration Rate; Humans; Hypoxia; Lung Diseases, Obstructive; Middle Aged; Osmolar Concentration; Sodium; Vasopressins; Water

Exogenous vasopressin decreases blood flow to the choroid plexus and production of cerebrospinal fluid. Some studies indicate that hypoxia and increases in intracranial pressure (ICP) produce increases in circulating vasopressin. We examined the hypothesis that endogenous release of vasopressin decreases blood flow to the choroid plexus during hypoxia and increased ICP. Blood flow to the choroid plexus was measured in anesthetized rabbits using microspheres. Hypoxia increased cerebral blood flow more than twofold but had little effect on blood flow to the choroid plexus. In contrast, hypoxia produced a marked increase in blood flow to the choroid plexus in the presence of a vasopressin V1-antagonist, [d(CH2)5Tyr(Me)]AVP. During intracranial hypertension, blood flow to the choroid plexus decreased from 409 +/- 42 to 295 +/- 25 ml.min-1 x 100 g-1 (means +/- SE; P < 0.05 vs. control) when ICP was increased from 1 to 40 mmHg. The vasopressin antagonist inhibited the decrease in blood flow to the choroid plexus in response to increased ICP. Thus release of vasopressin during hypoxia and increased ICP have a constrictor effect on blood vessels of the choroid plexus. Plasma levels of vasopressin increased minimally during hypoxia and increased ICP, which suggests that sources of vasopressin other than plasma affect blood vessels of the choroid plexus. We propose that endogenous vasopressin may play a protective role during hypoxia and intracranial hypertension by a negative feedback mechanism to reduce blood flow to the choroid plexus.

Topics: Animals; Arginine Vasopressin; Choroid Plexus; Feedback; Hypoxia; Intracranial Pressure; Microspheres; Pseudotumor Cerebri; Rabbits; Regional Blood Flow; Vasopressins

Hypothalamic mechanisms of neurohormone regulation of endocrine pancreas in diabetes mellitus, adaptation to hypoxia and their combination were studied on Wistar rats. To evaluate the condition of supraoptic nucleus (SON) secretory function, paraventricular subnuclei (PVH) of hypothalamus and endocrine pancreas, we used radioimmunoassay, immunocytochemical, morphometrical and histochemical methods. Hyperglycemia, hypoinsulinemia, glucagon and somatostatin synthesis and secretion intensification in diabetes mellitus is accompanied by marked reorganization of hypothalamic neurohormones (CRF, vasopressin, oxytocin) secretion with corresponding signs of activity increase of synthesizing their hypothalamus nuclei and subnuclei and also ACTH, corticosterone, cortisol rise in blood. Adaptation to hypoxia caused hypoglycemia, activated insulin biosynthesis, changed glucagon and somatostatin synthesis and secretion. CRF concentration, corticosterone and cortisol, ACTH in blood was not changed, vasopressin concentration lowered, oxytocin in median eminence of hypothalamus increased to a higher degree than in diabetes. Adaptation to hypoxia corrected impaired hormone balance and state of Langerhans islets (beta-cells destruction process inhibition, insulin biosynthesis stimulation, glucagon and somatostatin secretion decrease) in diabetes mellitus, hypothalamic neurohormones participating in this process.

Topics: Adaptation, Physiological; Animals; Blood Glucose; Corticotropin-Releasing Hormone; Diabetes Mellitus, Experimental; Glucagon; Hypothalamus; Hypoxia; Insulin; Islets of Langerhans; Oxytocin; Rats; Rats, Wistar; Somatostatin; Vasopressins

Vasopressin in cerebrospinal fluid has been measured in 27 fullterm newborns with hypoxic-ischemic encephalopathy. These newborns were divided into three groups according to the degree of neurological involvement, and they have been compared with a control group of 10 newborns. Determinations of vasopressin in cerebrospinal fluid and plasma were done by RIA. The cerebrospinal fluid vasopressin in asphyxiated newborns was higher than in the control group (p < 0.001); the mean concentration in the group of newborns classified as moderate or severe hypoxic-ischemic encephalopathy was higher than in the control group (18.7 pg/ml vs 4.66 pg/ml), and also higher than in the group classified as mild (14.2 pg/ml). Cerebrospinal fluid vasopressin values have a direct relationship to the plasmatic values at 12 hours of life (r = 0.76; p < 0.001). We concluded that vasopressin values in cerebrospinal fluid at 12 hours increase according to the clinical severity of the neonatal hypoxic-ischemic encephalopathy and that they have a strong relationship with plasmatic vasopressin.

Topics: Asphyxia Neonatorum; Brain Diseases; Brain Ischemia; Gestational Age; Humans; Hypoxia; Infant, Newborn; Vasopressins

To investigate whether central vasopressin play a role in the maintenance of cardiovascular activities of rats exposed to acute hypoxia, blood pressure, heart rate, pressures of left and right ventricles and their dp/dt were monitored in rats anesthetized with urethane. The rats were divided into three groups, each of which received intracerebroventricular injection (icv.) of V1- and V2-vasopressinergic antagonists (4 micrograms, each) and equivolumetric vehicle (8 microliters, served as control group). Ten min after icv. three groups of rats were exposed to acute hypoxia (9% O2 in N2) for 15 min before reoxygenation. During hypoxia, MBP, HR, LVSP and LV + dp/dtmax of V1-antagonist treated group decreased more significantly than those of the control group (P < 0.01). After reoxygenation there were no significant differences between both groups. V1-antagonist and the vehicle had no detectable effect on the cardiovascular parameters during normoxia. Although icv. V2-antagonist caused a transient augmentations of HR, MBP, LVSP and LV + dp/dtmax except for RVSP and RV + dp/dtmax, there were no significant differences in cardiovascular activities between V2-antagonist treated group and control group during hypoxia and reoxygenation. These results indicate that central endogenous vasopressin play an important role in the maintenance of cardiovascular activities during hypoxia via its V1-receptor without involving V2-receptor. The central vasopressin does not have a tonic effect on cardiovascular activities under normal conditions.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Heart Rate; Hypoxia; Injections, Intraventricular; Male; Rats; Rats, Sprague-Dawley; Vasopressins

1. In spontaneously breathing rats anaesthetized with Saffan, we have investigated the role of vasopressin in the cardiovascular responses evoked by systemic hypoxia (breathing 8 or 6% O2 for 5 min). 2. Breathing 8% O2 evoked an increase in respiratory frequency and tidal volume; arterial O2 pressure (Pa,O2) fell to 37 mmHg and arterial CO2 pressure (Pa,CO2) fell to 30 mmHg. Concomitantly, there was a fall in arterial pressure, tachycardia and increases in femoral and renal vascular conductances indicating net vasodilatation in skeletal muscle and kidney. The vasopressin V1-receptor antagonist, d(CH2)5Tyr(Me)-arginine vasopressin (20 micrograms kg-1 i.v.), had no significant effect on the baseline values of any recorded variables, nor on the respiratory or blood gas changes evoked by 8% O2. However, it accentuated the fall in arterial pressure and the increase in femoral vascular conductance (+22 vs. +77% at the 5th minute) produced by 8% O2, but had no significant effect on the increase in renal vascular conductance. 3. Breathing 6% O2 evoked qualitatively similar responses as 8% O2 but Pa,O2 fell to 33 mmHg and Pa,CO2 fell to 28 mmHg and the respiratory and cardiovascular changes tended to be larger than those evoked by 8% O2. Again the V1-receptor antagonist accentuated the hypoxia-induced fall in arterial pressure and increase in femoral vascular conductance (+5 vs. +76% at the 5th minute). 4. Infusion of vasopressin (1.5 ng min-1 kg-1 i.v.) for 5 min with the aim of producing a plasma concentration comparable to that reached during 8% O2, induced a rise in arterial pressure (9%), bradycardia (-5%) and a decrease in femoral (-11%) and renal vascular conductance (-4%). 5. These results suggest that vasopressin released during hypocapnic hypoxia helps to limit the evoked fall in arterial pressure by exerting a vasoconstrictor influence on skeletal muscle.

Topics: Anesthesia; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Heart; Hemodynamics; Hypothalamus; Hypoxia; Male; Rats; Rats, Wistar; Regional Blood Flow; Respiration; Vasopressins

1. In rats anaesthetized with Saffan, the spinotrapezius muscle was prepared for in vivo microscopy. Systemic hypoxia (breathing 8% O2 for 3 min) induced a fall in arterial pressure and tachycardia, together with constriction in some arterioles and venules of each section of the vascular tree and dilatation in others. 2. The vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)-arginine vasopressin (20 mg kg-1 I.V.) preferentially attenuated constrictor responses induced by hypoxia in both arterioles and venules, but had no significant effect on the dilator responses. Analysis of responses in individual sections of the vascular tree suggested that the V1-receptor antagonist reduced hypoxia-induced constrictor responses in proximal arterioles (> 13 microns diameter) though not in terminal arterioles (< 13 microns), but reduced hypoxia-induced constrictor responses in both the proximal and distal venules (9-130 microns). 3. Infusion of vasopressin at 1.4, 2.8, 5.7 and 11.4 ng min-1 kg-1 i.v. for 3 min, expected to produce plasma concentrations within the range 28-228 pg ml-1, evoked rises in arterial pressure together with decreases in heart rate. There was also vasoconstriction in the proximal arterioles of spinotrapezius that was graded with vasopressin concentration (5-35% decrease in diameter). 4. Infusion of vasopressin at 1.4 mg min-1 kg-1 i.v. for 3 min with the intention of producing a plasma concentration likely to be reached or exceeded during 8% O2, evoked constriction of all proximal arterioles, though not of terminal arterioles, and constriction of all venous vessels. The magnitude of the constriction induced by vasopressin in vessels that dilated during hypoxia was just as great as in those that constricted during hypoxia. 5. We propose that vasopressin released during systemic hypoxia exerts a constrictor influence upon the proximal arterioles and all sections of the venous tree of skeletal muscle. In individual arterioles and venules the constrictor influence of vasopressin and catecholamines may be overcome by the influence of locally released vasodilator metabolites.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Arterioles; Blood Pressure; Heart Rate; Hypoxia; Infusions, Intravenous; Male; Muscles; Rats; Rats, Wistar; Vasoconstriction; Vasopressins; Venules

We determined, in urethan-anesthetized rabbits, whether pharmacological alteration of neuronal function in the ventrolateral medulla oblongata, including the A1 area, and in the nucleus tractus solitarii (NTS), alters plasma adrenocorticotropic hormone (ACTH) and vasopressin and whether inhibition of neuronal function in the ventrolateral medulla impairs the secretion of ACTH normally observed in response to hemorrhage or constriction of the inferior vena cava. We also tested whether the increase in plasma ACTH and vasopressin after pharmacological inhibition of neuronal function in the NTS is dependent on a pathway that synapses in the A1 area of the ventrolateral medulla. Activation of the A1 area with bicuculline increased both ACTH and vasopressin. Inhibition of the NTS with muscimol increased levels of both hormones, as did hemorrhage and constriction of the inferior vena cava. Inhibition of neuronal function within the A1 area with muscimol eliminated the secretion of vasopressin but did not significantly alter the secretion of ACTH, obtained by injecting muscimol into the NTS. Injection of muscimol into the A1 area eliminated the secretion of both ACTH and vasopressin in response to constriction of the inferior vena cava and, in the case of vasopressin, in response to hemorrhage. Although hemorrhage-initiated secretion of ACTH was significantly reduced by injection of muscimol into the A1 area, it was not completely eliminated by these injections or by injections of muscimol into a more rostrocaudally extensive region of the medulla oblongata. We conclude that the net output from the NTS tonically inhibits secretion of both ACTH and vasopressin, reflecting tonic baroreceptor tone. For vasopressin, the pathway from the NTS to the hypothalamus is dependent on a synapse in the A1 area. For ACTH, there are pathways to the hypothalamus that do not synapse in the A1 area, but neurons in this region do have an excitatory effect on secretion of ACTH.

Topics: 2-Amino-5-phosphonovalerate; Adrenocorticotropic Hormone; Animals; Cardiovascular System; Constriction, Pathologic; Hemorrhage; Hypercapnia; Hypoxia; Injections; Medulla Oblongata; Muscimol; Rabbits; Stimulation, Chemical; Vasopressins; Vena Cava, Inferior

Cerebral blood flow (CBF) and cerebral utilization of oxygen (CMRO2) were studied in anesthetized and artificially ventilated rats during normoxemia and hypoxemia before and during intravenous infusion of a selective blocker of V2 vasopressinergic receptors (d(CH2)5 [D-Ile2,Abu4] AVP, 15 micrograms/kg per hour i.v.). CBF was measured by means of the intracarotid 133-Xe injection method. CMRO2 was calculated from the oxygen arteriovenous difference using the Fick principle. Infusion of V2 antagonist did not influence CBF, CMRO2 or blood pressure (BP) during normoxia. It also did not change the response of cerebral circulation to hypoxemia. Increase in CBF and decrease in cerebrovascular resistance (CVR) during hypoxemia were similar during the infusion of V2 blocker or without it. However, the decrease in BP observed during hypoxemia in the control group of rats was prevented in the group of animals which were infused with V2 blocker.

Topics: Angiotensin Receptor Antagonists; Animals; Arginine Vasopressin; Blood Pressure; Brain; Cerebrovascular Circulation; Hypoxia; Male; Oxygen Consumption; Rats; Rats, Wistar; Receptors, Angiotensin; Receptors, Vasopressin; Vascular Resistance; Vasopressins

This study investigated the accuracy of laser-Doppler flowmetry (LDV) and reflectance spectrophotometry (RS) measurements as an index of blood flow in the gastric mucosa of the rat, in experimental conditions such as pharmacologically induced vasoconstriction, hypoxia, hyperoxia, and acute normovolemic anemia. Hydrogen gas clearance was used as a reference method. After vasopressin infusion, LDV signal and indexes of hemoglobin (IHb) and oxygen (ISO2) content in the gastric mucosa estimated by RS significantly decreased in parallel with the reduction of gastric mucosal blood flow (GMBF). Neither hypoxia (5% O2 administration) nor hyperoxia (100% O2) affected GMBF or LDV signal. However, both IHb and ISO2 significantly decreased or increased after hypoxia or hyperoxia, respectively. Acute normovolemic anemia induced a significant increase in GMBF, while LDV signal and ISO2 remained unchanged. IHb significantly decreased in linear relationship with the decrements in the hematocrit. It is concluded that 1) in pharmacologically induced GMBF changes, LDV and RS correlate with GMBF; 2) when changes in hemoglobin saturation are induced, LDV but not RS reflects GMBF; and 3) in acute normovolemic anemia, neither LDV nor RS reflects changes in GMBF.

Topics: Anemia; Animals; Evaluation Studies as Topic; Gastric Mucosa; Hypoxia; Laser-Doppler Flowmetry; Male; Oxygen; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Spectrophotometry; Vasopressins

1. The aim of the present study was to determine the effect of water restriction and/or hypoxia on the vasopressin response to haemorrhage in conscious rats. 2. Male, Long-Evans rats (n = 39) were prepared with chronically indwelling femoral artery and vein catheters and exposed to 24 h of one of the following: normoxia with ad lib drinking water (N + W); normoxia with water restriction (N - W); hypoxia with ad lib drinking water (H + W); and hypoxia with water restriction (H - W). At the end of 24 h, a 15 mL/kg arterial haemorrhage was performed. 3. Water restricted rats had elevated pre-haemorrhage vasopressin levels. Haemorrhage induced an increase in vasopressin in all groups. Water restriction (N - W) or hypoxia (H + W) each augmented the vasopressin response to haemorrhage. However, the combination of hypoxia and water restriction (H - W) failed to augment the vasopressin response to haemorrhage as compared to normoxic, water replete (N + W) rats. 4. Hypoxia or water restriction per se augment the vasopressin response to haemorrhage. This augmented vasopressin response to haemorrhage is not maintained when hypoxia and water restriction are combined.

Topics: Animals; Blood Pressure; Hemorrhage; Hypoxia; Male; Rats; Rats, Inbred Strains; Vasopressins; Water Deprivation

To evaluate the role of vasopressin in the renal changes during combined acute hypoxemia and acute hypercapnic acidosis, eight conscious female mongrel dogs prepared with controlled sodium intake at 80 meq/24 h for 4 days were studied in one of the following six protocols: acute hypoxemia (80 min, arterial PO2 34 +/- 1 mmHg) followed by combined acute hypoxemia and hypercapnic acidosis (40 min, arterial PO2 35 +/- 1 mmHg, arterial PCO2 58 +/- 1 mmHg, pH = 7.20 +/- 0.01) during 1) intrarenal vehicle at 0.5 ml/min (N = 8); or 2) intrarenal infusion of vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP at 5 ng.kg-1.min-1 (N = 5); and with normal gas exchange during 3) intrarenal vasopressin at 0.05 mU.kg-1.min-1 (N = 8); 4) simultaneous infusion of intrarenal vasopressin and [d(CH2)5Tyr(Me)]AVP, 5 ng.kg-1.min-1 (N = 4); 5) intrarenal [d(CH2)5Tyr(Me)]AVP, 5 ng.kg-1.min-1 (N =4); and 6) intrarenal vehicle at 0.5 ml/min (N = 7). Intrarenal infusion of a subpressor dose of vasopressin resulted in a transient decrease in glomerular filtration rate and effective renal plasma flow over the first 20 min of infusion, suggesting that vasopressin induced nonsustained vasoconstriction of the renal vasculature. Intrarenal administration of [d(CH2)5Tyr-(Me)]AVP failed to block the fall in glomerular filtration rate or effective renal plasma flow when renal arterial blood vasopressin levels were elevated by intrarenal administration of exogenous vasopressin or by elevated systemic arterial endogenous circulating vasopressin during combined acute hypoxemia and hypercapnic acidosis. These data suggest that vasopressin (V1-receptor stimulation) does not play an important role in the renal vasoconstriction during combined acute hypoxemia and hypercapnic acidosis in conscious dogs.

Topics: Acidosis; Animals; Arginine Vasopressin; Dogs; Female; Hypercapnia; Hypoxia; Injections; Kidney; Receptors, Angiotensin; Receptors, Vasopressin; Reference Values; Renal Circulation; Vasopressins

The purpose of this study was to determine the effect of water restriction on the vasopressin response to hypoxia in conscious Long-Evans rats. Rats were prepared with chronic indwelling femoral artery and vein catheters 1 week before experimentation. At 24 h before the first blood sample, the supply of drinking water was maintained ad libitum (water replete) or removed (water deplete). At 24 h, a control blood sample was taken and then normoxia (21% O2) was maintained or hypoxia (10% O2) induced. Additional blood samples were taken at 1, 18 and 24 h. All blood samples (2.5 ml) were simultaneously replaced with donor blood to maintain isovolaemia. Hypoxia led to a very small and transient increase in vasopressin in the water-replete rats. The combination of hypoxia and water restriction led to a greatly augmented vasopressin response at 1 h (60 +/- 16 pmol/l); this response was also not sustained. Additional non-cannulated rats were exposed to 24 h of normoxia or hypoxia with or without water available ad libitum and posterior pituitaries were collected after decapitation for measurement of vasopressin content. Water restriction, hypoxia and water restriction plus hypoxia all led to decreased pituitary vasopressin content. We conclude that the vasopressin response to hypoxia in conscious rats is small and transient, and that concomitant water restriction augments the vasopressin response to acute but not chronic hypoxia.

Topics: Animals; Hypoxia; Male; Osmolar Concentration; Pituitary Gland; Rats; Rats, Inbred Strains; Vasopressins; Water Deprivation

Blood pressure is usually well maintained during epidural or spinal anesthesia even in the presence of extensive sympathetic blockade. The authors investigated whether hormonal systems support arterial pressure and how the circulation copes with a hypoxic challenge when activation of the sympathetic nervous system is selectively impaired by neural blockade. Accordingly, the effects of high epidural anesthesia alone and combined with hypoxia were evaluated in seven awake trained dogs. On different days, either bupivacaine 0.5% (8-12 ml) or saline (placebo) were randomly injected epidurally and the effects evaluated on cardiovascular (arterial pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, as well as on hormone plasma concentrations (vasopressin, norepinephrine, epinephrine, renin) during both normoxia and hypoxia. During epidural anesthesia alone, vasopressin increased tenfold (1.7 pg/ml +/- 1.0 SD to 16.8 +/- 13.8, P less than 0.05), norepinephrine decreased (90 pg/ml +/- 31 to 61 +/- 28, P less than 0.05) while epinephrine and renin concentrations remained unchanged. Mean arterial and pulse pressure decreased by 13 mmHg and 23 mmHg (P less than 0.05), respectively. In dogs without sympathetic blockade (saline group), hypoxemia (PaO2: 31 +/- 4 mmHg) evoked an increase in mean blood pressure by 37 mmHg +/- 8 and heart rate by 50 beats per min +/- 17. In contrast, in the presence of sympathetic blockade but with a similar degree of hypoxemia, blood pressure failed to increase (+ 1 mmHg +/- 14) and heart rate rose by only 15 beats per min +/- 11. These differences between groups were statistically significant (P less than 0.001). Hypoxemia induced a similar hypocarbia (PaCO2:25 mmHg) in both groups, indicating that the ventilatory response to hypoxemia was preserved after epidural blockade. During hypoxemia vasopressin concentrations increased 35-fold to 64 pg/ml +/- 38 (P less than 0.0001) compared to base line only during epidural anesthesia, but not after epidural saline (2 pg/ml +/- 2), while other hormones showed no significant differences. The authors conclude that high epidural anesthesia in awake unsedated dogs: 1) almost completely abolishes the normal cardiovascular response to hypoxemia while promoting vasopressin secretion; 2) preserves the ventilatory response to hypoxemia; and 3) is associated with increased vasopressin concentrations, most likely to compensate for decreased cardiac filling and/or arterial bl

Topics: Anesthesia, Epidural; Animals; Bupivacaine; Dogs; Epinephrine; Hemodynamics; Hypoxia; Norepinephrine; Renin; Sympathetic Nervous System; Vasopressins

In studies on the role of the peripheral sympathetic system during fetal life the effects of adrenal demedullation or chemical sympathectomy on the responses of the fetal sheep to hypoxaemia have been studied. Fetal sheep of 127-138 days gestation were either adrenal demedullated by injection of acid formalin into the adrenal medulla, chemically sympathectomised by chronic treatment with guanethidine sulphate, or subjected to both manipulations. None of these treatments had any effect upon resting heart rate and blood pressure, or blood gas status. Hypoxia was induced by giving the pregnant ewe 9% O2 and 3% CO2 in N2 to breathe for 60 min. This depressed fetal PO2 by about 30% in the intact and all but the adrenal-demedullated, chemically-sympathectomised fetuses, where the fall was about 50%. Similarly in this group of fetuses there was a sharp fall in plasma pH contrasting with little change in the other fetuses. Adrenal demedullation blocked completely the hypoxia-induced rise in fetal plasma adrenaline, and reduced that of noradrenaline to 10% of normal, implying that during hypoxia most of the plasma elevation of catecholamines is of adrenal origin. In contrast, and possibly to compensate for the blunted catecholamine response, plasma AVP increases during hypoxia were substantially enhanced by adrenal demedullation. Fetal hypoxia was associated normally with a fall in heart rate and rise in blood pressure. Adrenal demedullation had no effect on the heart rate changes, thought to be a reflex response to rise in blood pressure, but abolished the rise in blood pressure during hypoxia. Chemical sympathectomy, in contrast, abolished the fall in heart rate even though blood pressure rose. This shows clearly that reflex changes in heart rate during hypoxia can be uncoupled from those in blood pressure. Turning to the endocrine effects of demullation, cortisol and ACTH responses to hypoxia were much increased, whilst those of insulin were depressed. During chemical sympathectomy these responses were much accentuated in the case of cortisol and ACTH but depressed for insulin. A feature of these effects was that the endocrine changes in the adrenal-demedullated fetuses, whilst initially high, were not sustained for the 60 min of hypoxia. The same was true of the fetal matabolic responses to hypoxia reflected in plasma glucose, lactate and non-esterified fatty acids. Most of the results in this study are consistent with the proposal that in the fetus adrenal ca

Topics: Adrenal Medulla; Adrenocorticotropic Hormone; Animals; Blood Gas Analysis; Blood Glucose; Blood Pressure; Catecholamines; Embryonic and Fetal Development; Fatty Acids, Nonesterified; Heart Rate; Hydrocortisone; Hydrogen-Ion Concentration; Hypoxia; Insulin; Lactates; Lactic Acid; Peripheral Nerves; Sheep; Sympathetic Nervous System; Vasopressins

Hypoxia alters the relationship of aldosterone secretion to plasma renin activity. The potential role plasma electrolytes play in this modification is not clear. This study analyzed the interrelationships among renin, aldosterone, vasopressin (ADH), and plasma electrolytes during 96 h of normobaric hypoxia. Eight ewes were exposed, in discrete experiments, to hypocapnic hypoxia [arterial O2 tension (PaO2) 37-42 mmHg, arterial CO2 tension (PaCO2) 26-28 mmHg] and eucapnic hypoxia (PaO2 40-43 mmHg, PaCO2 28-31 mmHg) by N2 dilution in an environmental chamber. Urine output (24 h) was measured, and arterial plasma samples were collected during the normoxic control period and at 24-h intervals of hypoxia. Plasma Na+, K+, renin, and ADH levels did not change from the normoxic values during either hypocapnic or eucapnic hypoxia. However, urinary aldosterone excretion [critical significance (alpha) less than 0.046] and K+ excretion (alpha less than 0.046) decreased markedly during each type of hypoxia. All sheep developed a pronounced negative K+ balance by 96 h of hypoxia. These data suggest that plasma K+ concentration is preserved by movement of K+ out of the intracellular compartment; this change in K+ distribution may inhibit aldosterone secretion during hypoxia.

Topics: Aldosterone; Animals; Creatinine; Electrolytes; Female; Hypoxia; Kinetics; Models, Biological; Osmolar Concentration; Reference Values; Renin; Sheep; Time Factors; Urine; Vasopressins; Water-Electrolyte Balance

It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AVP) during intrauterine hypoxia/asphyxia reflects decreases in PaO2 and/or pHa; however, the components of these "stresses," i.e. PO2, PCO2, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PCO2. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 +/- 4 (mean +/- SD) days gestation with 1 M NH4Cl, while monitoring mean arterial pressure, heart rate, PaO2, PaCO2, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, PaO2, PaCO2, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 +/- 0.01 to 7.04 +/- 0.05 (p less than 0.05) during NH4Cl and did not return to control levels until 24 h later. AVP increased from 2.85 +/- 0.23 to 5.26 +/- 1.11 microU/ml (p less than 0.05) at the time of maximum acidosis, correlating with the fall in pHa (r = -0.67, (p = 0.001); however, after stopping NH4Cl, AVP returned to baseline levels although pHa remained less than 7.15. In control studies using the same osmolar load, volume, and rate of infusion, AVP levels were unchanged. Only epinephrine was significantly (p less than 0.05) elevated during acidosis, but did not correlate with pHa or plasma AVP. Marked metabolic acidemia appears to have little or no effect on fetal AVP secretion, and fetal catecholamine secretion is variable.

Topics: Acidosis; Ammonium Chloride; Amniotic Fluid; Animals; Arginine Vasopressin; Blood Gas Analysis; Catecholamines; Dopamine; Epinephrine; Female; Fetus; Hypoxia; Norepinephrine; Pregnancy; Sheep; Vasopressins

Six healthy volunteers were studied by use of a continuous ambulatory recording technique to document the normal range and variability of pulmonary artery pressure (PAP) and to examine its relationship to systemic arterial pressure (SAP) both at rest and during standardized interventions. Vasoactive hormone levels were measured at frequent intervals. Over 8-10 h of study the mean PAP was 15.7/6.3 mmHg. Parallel changes in PAP and SAP were observed at rest and during exercise and eating. On the contrary, PAP rose and SAP fell with hypoxia, whereas smoking was associated with a rise in SAP but no change in PAP. Sympathetic nervous system activity, as gauged by plasma norepinephrine levels, may have contributed to pressure and heart rate changes during exercise and smoking, but activity of the renin-angiotensin system was not altered by any of the maneuvers. These results provide base-line information on the level of PAP and its variability in healthy volunteers under standardized conditions. Pressures within the systemic and pulmonary circuits change in parallel under some circumstances but move in opposite directions under other conditions.

Topics: Adult; Aldosterone; Angiotensin II; Blood Gas Analysis; Blood Pressure; Blood Pressure Determination; Eating; Epinephrine; Female; Heart Rate; Humans; Hydrocortisone; Hypoxia; Male; Norepinephrine; Peptidyl-Dipeptidase A; Physical Exertion; Pulmonary Artery; Reference Values; Renin; Renin-Angiotensin System; Smoking; Vasopressins

We investigated the antidiuretic hormone (ADH) response in 12 infants with bronchopulmonary dysplasia during acute respiratory distress. All of the infants had hypoxemia with air-trapping in the chest at the time of admission to the hospital. None had documented infection. There was a dramatic increase in the plasma levels of ADH during acute respiratory distress, with a subsequent reduction of levels toward normal when the respiratory distress decreased to the preadmission well state. Three of 12 infants manifested hyponatremia at 24 hours after admission, with two of them exhibiting persistent hypertension for up to three days. The mechanism for elevated ADH levels is air-trapping in the chest, causing pulmonary hypovolemia and decreased left atrial filling and/or decreased transmural pressure of the left atrium.

Topics: Bronchopulmonary Dysplasia; Female; Furosemide; Humans; Hyponatremia; Hypoxia; Infant; Infant, Newborn; Male; Respiratory Distress Syndrome, Newborn; Vasopressins

The effect of neuropeptides and their analogs on anoxia-induced amnesia was examined using one-trial passive avoidance task in mice. Anoxia, produced by the exposure to CO2 immediately after the acquisition of avoidance response, induced amnesia which is shown by a short latency to enter from the safety compartment into the shocked compartment in the retention test conducted 24 hr later. In these anoxia-treated animals, thyrotropin-releasing hormone (TRH: 10-20 mg/kg), its analog DN-1417 (10-20 mg/kg) and ACTH 4-10 (66 micrograms/body), which were given sc 15-60 min before the retention test, markedly prolonged the latency in a dose-dependent manner, indicating a reversal of the amnesia. Arginine- and lysine-vasopressin also reversed the amnesia at a dose of 100 micrograms/body. These results suggest that TRH and DN-1417, known to reverse the amnesia produced by the protein synthesis inhibitor cycloheximide, have ameliorating effects on the retrieval process of memory.

Topics: Adrenocorticotropic Hormone; Amnesia; Animals; Hypoxia; Male; Memory; Mice; Thyrotropin-Releasing Hormone; Vasopressins

Vasopressin (VP) has been found in the cerebrospinal fluid (CSF) of several species of animals. Although it is known that hemorrhage, hypertonicity of body fluid, hypoxia, and hypercapnia all increase VP in plasma, little is known regarding the stimuli that cause the secretion of VP into the CSF. We therefore performed several studies to examine whether stimuli capable of increasing plasma levels of VP can also increase VP in the CSF of anesthetized dogs. We found that hemorrhage, intracerebroventricular infusion of hypertonic artificial CSF, hypoxia, and hypercapnia all produced increases in the concentration of VP in plasma and in CSF, but the time courses and the magnitude of the increases in the two compartments were different. In addition, an i.v. infusion of hypertonic saline or of hydrochloric acid produced an increase in plasma VP without significantly changing CSF VP. Thus, although the secretion of VP into plasma and CSF may be influenced by the same stimuli, changes in one compartment do not necessarily correlate with changes in the other. Taken together, our results are consistent with the hypothesis that the plasma and CSF VP may derive from different sources.

Topics: Acidosis; Animals; Cerebrospinal Fluid; Dogs; Hemorrhage; Hypercapnia; Hypoxia; Infusions, Parenteral; Injections, Intraventricular; Saline Solution, Hypertonic; Vasopressins

Vasopressin has been found to significantly decrease tissue pO2 in the gastrointestinal tract and the liver. The aim of this study was to find out whether 60% oxygen ventilation could prevent the tissue hypoxia. Vasopressin was infused i.v. in ten piglets for 60 min. During the first 30 min they were ventilated by room air and for the following 30 min by 60% oxygen, which did not alter the intestinal tissue pO2, but liver pO2 increased to the normal level. The plasma lactate was significantly decreased by 60% oxygen ventilation. The findings in this experimental study suggest that 60% oxygen ventilation is indicated in the clinical use of vasopressin infusion.

Topics: Animals; Carbon Dioxide; Hypoxia; Intestine, Small; Lactates; Lactic Acid; Liver; Oxygen; Swine; Vasopressins

Hypoxia and hypercapnia have been shown to cause an increase in the concentration of vasopressin in plasma, but their effects on vasopressin in cerebrospinal fluid (CSF) are not known. In addition, the effect of metabolic acidosis on plasma and CSF vasopressin has not been reported. In this study, plasma and CSF vasopressin levels were measured in anesthetized dogs subjected to either hypoxia, hypercapnia, or metabolic acidosis. Rate and depth of respiration were closely regulated with the aid of muscle paralysis and mechanical ventilation. Vasopressin increased markedly in both plasma and CSF during severe hypoxia (10% O2) and during hypercapnia (10% CO2) but did not change during either mild (15% O2) or moderate (12.5% O2) hypoxia. Although mild hypoxia by itself did not affect either plasma or CSF vasopressin, it did potentiate the increase in plasma and CSF vasopressin that was induced by severe hypercapnia, thus suggesting that hypoxia and hypercapnia may exert synergistic effects on vasopressin secretion. Metabolic acidosis produced by slow intravenous infusion of 1 N hydrochloric acid decreased arterial pH to values comparable to those induced by hypercapnia and increased vasopressin in plasma; CSF vasopressin was unchanged. These results are consistent with the concept that the source of vasopressin secreted into plasma may be different from that secreted into CSF.

Topics: Acidosis; Animals; Dogs; Hypercapnia; Hypoxia; Vasopressins

The factors associated with increased renal excretion of vasopressin (VP) were examined in the hypoxic fetus and newborn. Studies were conducted on six chronically instrumented fetal (117-136 days gestation) and seven newborn lambs (2-6-day-old). Hypoxia was produced by administration of 10% oxygen to the ewe or neonate for 30 min. This procedure caused a 50% reduction in PaO2, no significant change in pHa in either fetus or neonate and a slight fall in PaCO2. Hypoxia caused an increase in VP concentrations in plasma from 1.3 +/- 0.53 to 46.4 +/- 4.71 pg/ml in the fetus and from 5.9 +/- 2.80 to 50.2 +/- 26.68 pg/ml in the neonate. After hypoxia there was a fall in urine output from 0.27 +/- 0.045 to 0.17 +/- 0.046 ml/(min X kg) in the fetus and from 0.15 +/- 0.033 to 0.09 +/- 0.022 ml/(min X kg) in the newborn. The corresponding values for urine osmolality were the following: 168 +/- 30.8 to 325 +/- 30.6 mOsm/kg in the fetus and 388 +/- 65.4 to 523 +/- 51.8 mOsm/kg in the newborn. VP concentration in urine increased from 13 +/- 9.4 to a maximum of 176 +/- 32.4 pg/ml after 30 min of recovery in the fetus and 39 +/- 4.6 to 278 +/- 132.5 pg/ml after 1 h of recovery in the newborn. These levels remained high for at least 1 h after the end of hypoxia. There was a good linear correlation between plasma VP levels and the corresponding urine levels and excretion rates in both the fetus and newborn.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Female; Fetal Hypoxia; Glomerular Filtration Rate; Hypoxia; Kidney Concentrating Ability; Natriuresis; Pregnancy; Sheep; Vasopressins

The relationship between concentrations of vasopressin in plasma and cerebrospinal fluid (CSF) was examined under basal and hypoxic conditions in unanesthetized and unrestrained adult female sheep. Under basal conditions mean (+/- SE) concentration of vasopressin (4.1 +/- 0.3 pg/ml) in CSF was significantly (p less than 0.001) higher than the concentration in arterial plasma (2.4 +/- 0.2 pg/ml). There was a significant positive correlation between CSF and plasma vasopressin concentrations (r = 0.66, p less than 0.01). The introduction of severe hypoxia by exposure of the sheep to an inspired gas mixture of 5% O2 in N2, a known stimulus to systemic release of vasopressin, was associated with an increase in the concentration of vasopressin in plasma to 339 +/- 65 pg/ml and CSF to 19 +/- 3.9 pg/ml. This increase of vasopressin in CSF was delayed in time with respect to the increases in the plasma and of a lesser magnitude. With moderate hypoxia (10% O2 in N2 exposure) no increase in CSF or plasma vasopressin concentration was observed, suggesting a threshold response. Intravenous infusion of vasopressin to achieve plasma values comparable to those seen with hypoxia was not accompanied by a significant increase in CSF vasopressin concentration. Thus, severe hypoxia is a potent stimulus for release of vasopressin into both CSF and plasma. Furthermore, data suggest that vasopressin may be released into CSF via a separate route from that released into plasma.

Topics: Animals; Female; Hypoxia; Radioimmunoassay; Sheep; Time Factors; Vasopressins

To determine the effects of acute blood gas derangements on renal water and solute excretion and vasopressin secretion, six unanesthetized mongrel dogs were studied during 1) combined acute hypoxemia and hypercapnic acidosis [arterial O2 partial pressure (PaO2) 36 +/- 1 Torr, arterial CO2 partial pressure (PaCO2) 54 +/- 2 Torr, pH 7.18 +/- 0.01], 2) acute hypoxemia (PaO2 33 +/- 2 Torr, PaCO2 33 +/- 1 Torr, pH 7.34 +/- 0.01), and 3) acute hypercapnic acidosis (PaO2 83 +/- 3 Torr, PaCO2 53 +/- 1 Torr, pH 7.19 +/- 0.02). Combined acute hypoxemia and hypercapnic acidosis increased (P less than 0.05) mean arterial pressure, but renal hemodynamic function deteriorated with decreased (P less than 0.05) glomerular filtration rate and increased (P less than 0.05) renal vascular resistance. Moreover free water clearance became more negative (P less than 0.05) and urine osmolality increased (P less than 0.05). During acute hypoxemia or acute hypercapnic acidosis alone, mean arterial pressure and renal hemodynamic function were unchanged but free water clearance became more negative (P less than 0.05). During acute hypoxemia, urine osmolality increased (P less than 0.05) comparably with values observed during combined acute hypoxemia and hypercapnic acidosis. Plasma vasopressin concentrations increased profoundly (P less than 0.05) during combined hypoxemia and hypercapnic acidosis and during acute hypoxemia alone and were significantly elevated (P less than 0.05) above the increased plasma vasopressin concentrations observed during acute hypercapnic acidosis. We conclude that acute hypoxemia and hypercapnic acidosis result in impairment of renal water excretion, probably mediated through vasopressin secretion.

Topics: Animals; Arginine Vasopressin; Cardiac Output; Diuresis; Dogs; Female; Glomerular Filtration Rate; Heart Rate; Hypercapnia; Hypoxia; Kidney; Osmolar Concentration; Renal Circulation; Vascular Resistance; Vasopressins

Topics: Adrenal Glands; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Gas Analysis; Blood Pressure; Captopril; Glomerular Filtration Rate; Hypoxia; Kidney; Prostaglandins E; Renin; Sheep; Vasopressins

Topics: Acidosis; Female; Fetal Distress; Humans; Hypoxia; Pregnancy; Vasopressins

The relative effects of 3 stimuli in the release of vasopressin (VP) by the fetus were examined in 19 chronically instrumented fetal lambs, 118-135 days gestational age. The fetus was exposed to: 1) 30-min administration of 10% O2 to the pregnant ewe, 2) 20 min of partial occlusion of the umbilical cord, or 3) 2 min of complete occlusion of the umbilical cord. Twelve studies were conducted for each of these experimental protocols. The rises (mean +/- SE) in plasma VP in the 3 groups were 29.9 +/- 8.9, 48.9 +/- 11.5, and 157.8 +/- 12.5 pg/ml, respectively; the corresponding falls in PaO2 were 9.2 +/- 0.7, 7.7 +/- 0.9, and 12.7 +/- 1.2 mm Hg. pHa did not change in the group receiving 10% O2, fell by 0.11 +/- 0.02 and 0.14 +/- 0.01 after partial and complete occlusion of the umbilical cord. The rises in mean arterial pressure were 6 +/- 2.2, 10 +/- 1.9, and 23 +/- 3.1 mm Hg, respectively, at the end of the 3 procedures. The rise in plasma osmolality ranged from 2-8 mosmol/kg in all 3 groups. Linear regression analyses showed that log VP was negatively correlated with PaO2 (r = -0.827; P less than 0.01) and pHa (r = -0.706; P less than 0.01) and positively correlated to mean arterial pressure (r = 0.607; P = 0.01), but was not significantly correlated to plasma osmolality. Our present findings suggest that hypoxemia and acidemia are associated with and may both be potent stimuli for VP release in the hypoxic fetus. Increased release together with decreased rate of metabolism by the placenta offer an explanation for the very high VP levels found in the neonate after labor and delivery.

Topics: Acid-Base Imbalance; Animals; Blood Gas Analysis; Female; Fetal Blood; Fetus; Gestational Age; Hypoxia; Pregnancy; Sheep; Vasopressins

Lesions of the circumventricular organs were produced by administration of monosodium-L-glutamate to neonatal rats. At 16 weeks of age these rats were given different stimuli to vasopressin release. In control rats, morphine (50 micrograms) injected into the third ventricle resulted in a rapid increase in plasma vasopressin concentrations at 10 min, followed by a reduction at 20 min. The circumventricular organ-lesioned rats, however, showed a pronounced fall in vasopressin secretion both at 10 and 20 min after 50 micrograms morphine. A similar abolition of the morphine-elicited rise in plasma vasopressin could also be achieved by the iv infusion of small doses of dopamine in normal rats. Hypoxic stimuli, which result in a marked rise in vasopressin in normal rats, failed to elicit any increase in circumventricular organ-lesioned animals. Vasopressin release after stimulation with 9% saline, however, was augmented in the lesioned animals. These results suggest that circumventricular organs have an important role in controlling neurohypophyseal secretion and that they differentially control different stimuli to vasopressin release via dopaminergic and opiate pathways.

Topics: Animals; Animals, Newborn; Arginine Vasopressin; Dopamine; Female; Hypothalamus; Hypoxia; Male; Morphine; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Sodium Glutamate; Vasopressins

Release of antidiuretic hormone (ADH) due to hypoxic stimuli has been documented in several in vivo models. The current study was performed to determine whether 1) hypoxia causes ADH release in the conscious normovolemic dog and 2) whether endogenous prostaglandins are involved in hypoxic ADH release. Five conscious dogs were made hypoxic by inhalation of 10% O2. Dogs were studied both with and without pretreatment with meclofenamate (2 mg/kg iv and 2 mg . kg-1 . h-1). Hypoxic exposure resulted in elevated plasma ADH; however, meclofenamate totally blocked this response. Hemodynamic responses to hypoxia were unaffected by meclofenamate. In addition, plasma osmolality was unchanged by hypoxia in both groups. Since meclofenamate does not cross the blood-brain barrier, it is concluded that the release of ADH by hypoxia in the conscious dog may be mediated by endogenous prostaglandins produced outside the central nervous system. It appears that elevated renal prostaglandin release, increased ADH, and hemodynamic alterations could all interact to determine the final renal response to hypoxia.

Topics: Animals; Blood Pressure; Cardiac Output; Consciousness; Dogs; Female; Hypoxia; Meclofenamic Acid; ortho-Aminobenzoates; Vasopressins

To investigate the developmental changes in the secretion of vasopressin and the potential role of beta-endorphin as a stimulus to the release of vasopressin, the concentrations of these peptides were measured in fetal, newborn, and adult sheep after episodes of induced hypoxia. The studies confirm that hypoxia is a potent stimulus to the release of both vasopressin and beta-endorphin in the fetal animal. In both the newborn lamb and the ewe, more profound hypoxia is necessary for a similar release. In the fetus, the release of both vasopressin and beta-endorphin after hypoxia increased with gestational maturation. A comparison of control concentrations of both peptides, the discordance of release in the newborn lamb, and the absence of a change in concentrations of vasopressin with infusion of beta-endorphin implies that these hormones are released in parallel but independently during hypoxic stress.

Topics: Aging; Animals; beta-Endorphin; Endorphins; Female; Fetal Hypoxia; Fetus; Hypoxia; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Vasopressins

Urinary excretion rate of antidiuretic hormone (UADHV) was studied in male volunteers in response to hypobaric hypoxia. The first series consisted of three groups. The chamber was decompressed to 465, 495, and 438 Torr during high-altitude (HA) exposure for groups I (n = 5), II (n = 5), and III (n = 4), respectively. In group I, the chamber air contained 3.77% CO2 to prevent alkalosis. The level of hypoxemia was similar in groups I and II. Mean 24-h UADHV was unchanged in group I, but increased 96% (P less than 0.05) and 180% (P less than 0.05) in groups II and III, respectively, on day 1 at HA and was normal during subsequent days at HA regardless of symptoms of acute mountain sickness. Shorter sampling intervals employed in a second series of experiments conducted at 495 Torr revealed a twofold increase in UADHV (P less than 0.05) 8-12 h after ascent in eight asymptomatic subjects; UADHV returned to base line within 9 h and remained low. The symptomatic subjects both had increased UADHV (3- and 8-fold from base line) between 2 and 4 h after ascent. Increased UADHV in asymptomatic subjects may be a result of the concomitant decrease in plasma volume, both of which appeared to be eliminated by CO2 supplementation.

Topics: Adult; Blood Pressure; Carbon Dioxide; Humans; Hypoxia; Kidney; Male; Potassium; Regional Blood Flow; Sodium; Time Factors; Vasopressins

Topics: Acute Kidney Injury; Diagnosis, Differential; Humans; Hypoxia; Pulmonary Edema; Urethral Obstruction; Vasopressins

Topics: Adolescent; Brain Diseases; Diabetes Insipidus; Female; Humans; Hypoxia; Male; Middle Aged; Vasopressins

The level of antidiuretic hormone (ADH) in the plasma of pigs was studied during hypozia, anaesthesia and a combination of the two conditions. Hypoxia, caused by making conscious pigs breathe nitrogen, elicited a rise in the level of ADH without change in plasma osmolality; the hypoxia was accompanied in some cases by a slight lowering of arterial pressure which quickly returned to its original level after the period of hypoxic breathing. Pentobarbitone anaesthesia had no significant effect on the level of ADH but halothane anaesthesia elicited a rise in ADH. Transient high levels of ADH were seen in animals which were exposed to hypoxia during halothane or pentobarbitone anaesthesia. These high levels of ADH were sometimes, but not invariably, accompanied by a fall in arterial pressure. No consistent changes in plasma osmolality or haematocrit were associated with the raised plasma ADH.

Topics: Anesthesia; Animals; Blood Pressure; Halothane; Hematocrit; Hypoxia; Osmolar Concentration; Pentobarbital; Swine; Vasopressins

Topics: Animals; Haplorhini; Humans; Hypoxia; Infant, Newborn; Infant, Newborn, Diseases; Vasopressins

1. Fotetal plasma vasopressin levels were measured by bio-assay in chronically catheterized sheep from 110 to 145 days gestation. 2. In foetuses in good condition resting circulating vasopressin concentrations were generally undetectable (less than 5 micromicron./ml.). In 15% of the samples low concentrations (5-10 micromicron./ml.) were observed. 3. Hypoxaemia in the foetus was caused by allowing the ewe to breathe 9% O2-3% CO2 in N2 for 1 hr. Plasma vasopressin levels rose in the foetus to 119 +/- 32 micromicron./ml., whereas the hormone levels in the ewe were not routinely increased. In the foetus, the rise in plasma vasopressin levels was significantly related to the fall in pH and Pa, O2 during the hypoxia. 4. In foetuses in which the cervical vagosympathetic trunks were cut, the rise in plasma vasopressin levels (to 48 +/- 25 micromicron./ml.) during hypoxaemia was less than in intact foetuses. The increase was related only to the fall in arterial pH and the regression coefficient was less than in intact foetuses. 5. During hypoxaemia arterial pressure rose and heart rate fell in the normal foetuses. The rise in arterial pressure was greatest when the plasma vasopressin concentration was highest. 6. Spontaneous episodes of hypoxaemia (Pa, O2 less than 15 mmHg) and/or acidaemia (pH less than 7.30) occurred in four intact foetuses and four foetuses in which the cervical vagosympathetic trunks were cut; all of the latter lambs died in utero. Plasma vasopressin levels were elevated and the concentrations were inversely related to arterial pH. 7. Intravenous infusions of vasopressin to foetuses increased plasma vasopressin levels to 6-202 micromicron./ml.; the rate of clearance of the hormone was three times that in adult ewes. There was a large increase in arterial pressure and bradycardia. The hypertensive effects of vasopressin were relatively much greater in the foetus than in adult ewes.

Topics: Animals; Blood Pressure; Fetal Blood; Heart Rate; Hypoxia; Sheep; Vagotomy; Vasopressins

Eight men, 19-35 years of age, breathed 20.9% (normal oxygen), 13.9% (mild hypoxia) or 11.1% (severe hypoxia) oxygen in nitrogen gas mixtures during three 20 min periods, which were separated by 1 h recovery periods. The order in which the gas mixtures were breathed was random. The partial pressure of oxygen decreased from a mean of 93.5 during exposure to normal oxygen to 53.9 and 36.7 mmHg during mild and severe hypoxia respectively. There were corresponding decreases in haemoglobin saturation. The partial pressure of carbon dioxide was lower and the pH higher during severe hypoxia than during exposure to normal oxygen. There were no changes in the plasma osmolality or in the concentrations of sodium or potassium in the plasma. There was a tendency for both the renin activity and the concentration of aldosterone in the plasma to decrease progressively as the percentage of oxygen breathed decreased. Unlike severe hypoxia, mild hypoxia suppressed the concentration of antidiuretic hormone (ADH) in the plasma of all subjects by about 59%; during severe hypoxia the reduction was not significant, being only about 33%. These data are consistent with the suggestion that the effect of hypoxia on the release of ADH is dependent on the level of hypoxia.

Topics: Adult; Aldosterone; Diuresis; Humans; Hypoxia; Male; Renin; Vasopressins

The effect of lowering the pressure of oxygen from 80 to 34 mm Hg was examined in anesthetized dogs that were undergoing a water diuresis. This degree of hypoxia was associated with an antidiuresis as urine osmolality (Uosm) increased from 107 to 316 mosmol/kg H(2)O (P < 0.001) and plasma arginine vasopressin increased from 0.06 to 7.5 muU/ml, (P < 0.05). However, hypoxia was not associated with significant changes in cardiac output (CO, from 4.2 to 4.7 liters/ min), mean arterial pressure (MAP, from 143 to 149 mm Hg), glomerular filtration rate (GFR, from 46 to 42 ml/min), solute excretion rate (SV, from 302 to 297 mosmol/min), or filtration fraction (from 0.26 to 0.27, NS). Hypoxia was associated with an increase in renal vascular resistance (from 0.49 to 0.58 mm Hg/ml per min, P < 0.01). The magnitude of hypoxia-induced antidiuresis was the same in innervated kidneys and denervated kidneys. To further examine the role of vasopressin in this antidiuresis, hypoxia was induced in hypophysectomized animals. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in hypophysectomized animals was the same as in intact animals. In contrast to intact animals, however, hypoxia did not induce a significant antidiuresis in hypophysectomized animals (Uosm from 72 to 82 mosmol/kg H(2)O). To delineate the afferent pathway for hypoxia-stimulated vasopressin release, hypoxia was induced in dogs with either chemo- or baroreceptor denervation. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in the denervated animals was the same as in nondenervated animals. Hypoxia resulted in an antidiuresis in chemoreceptor (Uosm from 113 to 357 mosmol/kg H(2)O, P < 0.001) but not in baroreceptor (Uosm from 116 to 138 mosmol/kg H(2)O, NS) denervated animals. To determine if hypoxia alters renal response to vasopressin, exogenous vasopressin was administered to normoxic and hypoxic groups of dogs. The antidiuretic effect of vasopressin was no different in these two groups. These results demonstrate that hypoxia induces an antidiuresis which is independent of alterations in CO, MAP, SV, filtration fraction, renal nerves, or renal response to vasopressin and occurs through baroreceptor-mediated vasopressin release. The nature of the baroreceptor stimulation remains to be elucidated.

Topics: Animals; Carotid Body; Diuresis; Dogs; Female; Hypoxia; Kidney; Male; Osmolar Concentration; Pituitary Gland, Posterior; Vasopressins; Water-Electrolyte Balance

Aspects of the relationships between cellular composition and transepithelial sodium transport across toad urinary bladder are reviewed. Changes in cellular sodium produced by amiloride, vasopressin, aldosterone, hypoxia, ouabain, and sodium-free media are consistent with a cellular sodium transport pool. Metabolic studies suggest that this pool gains its sodium from the mucosal medium and that there is little recycling of sodium between cell and serosal medium. One-third of the cellular potassium equilibrates readily with serosal potassium. The rate of exchange of potassium is much less than the rate of sodium transport supporting the contention that sodium transport in this tissue is electrogenic. Studies with 36Cl suggest that chloride does not cross the apical cellular membranes, but exchanges with serosal chloride. Possible relationships between transepithelial sodium transport and cellular volume regulation are discussed.

Topics: Aldosterone; Amiloride; Animals; Anura; Biological Transport, Active; Cell Count; Chlorides; Dose-Response Relationship, Drug; Epithelial Cells; Epithelium; Hypoxia; In Vitro Techniques; Ouabain; Potassium; Sodium; Urinary Bladder; Vasopressins

Topics: Altitude; Altitude Sickness; Female; Humans; Hypoxia; Male; Vasopressins

Diabetes insipidus following cardiac arrest and hypoxemic encephalopathy occurred in two patients. In both, severe hypoxemic brain damage was followed within three days by clinical and laboratory features of diabetes insipidus, which were corrected by administration of exogenous vasopressin. Hypothalamic injury resulting in diabetes insipidus should be considered in the differential diagnosis of polyuria and dehydration occurring in critically ill patients who have suffered cardiorespiratory arrest.

Topics: Adult; Diabetes Insipidus; Female; Heart Arrest; Humans; Hypothalamus; Hypoxia; Hypoxia, Brain; Respiratory Insufficiency; Vasopressins

Topics: Humans; Hypoxia; Male; Vasopressins

1. Acute hypoxaemia had been reported to stimulate vasopressin release in animals. 2. Hypoxaemia induced by breathing 9-3% oxygen for 15-20 min failed to produce a rise in plasma arginine vasopressin concentration in six out of eight healthy human subjects. The two subjects who developed an increase in plasma arginine vasopressin concentration had a significant rise in serum cortisol. 3. Breathing 100% nitrogen until impairment of consciousness caused no rise in plasma arginine vasopressin concentration.

Topics: Adult; Arginine Vasopressin; Humans; Hydrocortisone; Hypoxia; Male; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Fetus; Hypoxia; Sheep; Vasopressins

The literature suggests that platelets might help mediate the pulmonary vascular pressor response to hypoxia. This study evaluated the hypoxic response in thrombocytopenic dogs. Platet depletion was achieved in five dogs by the use of platelet antiserum. In the normoxic state these dogs had lower cardiac outputs and higher pulmonary and systemic vascular resistances than five control dogs. The pressor response to hypoxia in these dogs was not only preserved but considerably enhanced in comparison to the control dogs. Hypoxia increased the pulmonary vascular resistance 146 +/- 17% above its normoxic value in the thrombocytopenic dogs and 64 +/- 21% in the control dogs. Thus platelets may normally produce a dilator substance or inactivate a pressor substance during hypoxia. The mechanism of the effect is not apparent but it is clear tha the pulmonary pressor response to hypoxia in the dog is not mediated by platelets.

Topics: Animals; Blood Cell Count; Blood Platelets; Blood Pressure; Cardiac Output; Dogs; Hypoxia; Lung; Prostaglandins F; Thrombocytopenia; Vascular Resistance; Vasopressins

The role of hyperthermia in the absence of infection has been investigated in the pregnant baboon. Twenty-three near term animals were used. Catheters were placed in maternal and fetal arteries and thermocouples implanted in maternal colon and fetal esophagus. Maternal temperature was raised to between 41 and 42 degrees Centigrade (C.), by applying external heat. The temperature gradient between fetus and mother (delta T F-M) was 0.47 degree C. under steady-state conditions with maternal temperature at 38 degrees C. and rose to 0.75 degree C. at 42 degrees C. Hyperthermia caused a twofold increase in uterine activity; a metabolic acidosis developed in the mother and a profound acidosis and hypoxia developed in the fetus. There was also a marked fall in blood pressure and an increase in heart rate in both mother and fetus; late deceleration of the fetal heart rate occurred at a higher oxygen level and pHa than has been observed under normothermic conditions.

Topics: Acidosis; Animals; Arrhythmias, Cardiac; Body Temperature; Female; Fetal Death; Fetal Diseases; Fetal Heart; Fever; Haplorhini; Heart Rate; Hypotension; Hypoxia; Labor, Obstetric; Oxytocin; Papio; Pregnancy; Pregnancy Complications; Vasopressins

Impaired water excretion has been described in stable, nonedematous patients with chronic obstructive lung disease (COLD). To elucidate the mechanism involved, we measured basal glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and water, sodium, and solute excretion for 4 hours after water loading (20 ml. per kilogram orally or as D5W intravenously) in two groups of 10 age-matched, hypoxic, stable, nonedematous COLD normocapneic and hypercapneic patients (PCO2 less than or greater than 45 mm. Hg, respectively). In 5 patients of each group, additional measurements of plasma and urine osmolality and plasma vasopressin were made at 30-minute intervals after oral water loading and the results compared to those obtained in 10 normal control subjects. Hypoxic (PO2 61 plus or minus 2 mm. Hg), normocapneic (PCO2 39 plus or minus 1 mm. Hg) patients had normal GFR (114 plus or minus 5 ml. per minute) and ERPF (517 plus or minus 31 ml. per minute) and excreted the load normally (101 plus or minus 5 per cent of oral or intravenous water per 4-hours). This was associated with a normal rate of sodium excretion (34 plus or minus 5 mEq. per 4-hours) and low-normal plasma vasopressin (1.9 plus or minus 0.7 pg. per milliliter) which was suppressed appropriately with water loading. Hypercapneic (PCO2' 62 plus or minus 5), hypoxic (PCO2' 57 plus or minus 2) patients had normal GFR (106 plus or minus 7), low baseline vasopressin (1.1 plus or minus 0.2) which was suppressed appropriately, and decreased (p less than 0.05) 4-hour water excretion (63 plus or minus 8 per cent), 4-hour sodium excretion (15 plus or minus 9), and ERPF (394 plus or minus 31). A significant correlation was observed between impaired water and impaired sodium excretion (p less than 0.05). These studies indicate that in COLD patients: (1) hypercapnia but not hypoxemia is related to the abnormal water handling and to the increased reabsorption of sodium by the renal tubule; (2) the defect in water excretion is not related to abnormal vasopressin secretion or metabolism; (3) the alteration in sodium excretion may be due to hypercapneic-induced increase in renal bicarbonate reabsorption and/or abnormal renal blood flow.

Topics: Adult; Arginine; Chronic Disease; Glomerular Filtration Rate; Humans; Hypercapnia; Hypoxia; Kidney; Lung Diseases, Obstructive; Middle Aged; Osmolar Concentration; Radioimmunoassay; Regional Blood Flow; Regression Analysis; Sodium; Urine; Vasopressins; Water; Water-Electrolyte Balance

Topics: Animals; Cats; Hypercapnia; Hypoxia; Vasopressins

Topics: Animals; Arginine; Blood Pressure; Dogs; Hypoxia; Male; Vasopressins

Topics: Animals; Body Weight; Dehydration; Drinking Behavior; Environment, Controlled; Environmental Exposure; Feeding Behavior; Hypothermia; Hypoxia; Kidney; Kidney Concentrating Ability; Male; Organ Size; Osmolar Concentration; Oxygen Consumption; Rats; Regression Analysis; Time Factors; Urination; Vasopressins; Water

Topics: Anesthesia; Animals; Arginine; Dogs; Hypotension; Hypoxia; Kidney Concentrating Ability; Osmolar Concentration; Pentobarbital; Sodium; Urination; Vasopressins

Topics: Acclimatization; Adult; Altitude; Blood Physiological Phenomena; Blood Specimen Collection; Chronic Disease; Extracellular Space; Humans; Hypoxia; Methods; Middle Aged; Osmolar Concentration; Peru; Sodium; Time Factors; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Antimycin A; Cold Temperature; Dinitrophenols; Ethylmaleimide; Hypoxia; In Vitro Techniques; Iodoacetates; Male; Oligomycins; Pituitary Gland; Rats; Vasopressins

Topics: Acid-Base Equilibrium; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Blood Glucose; Female; Fetal Heart; Fetus; Fructose; Heart Rate; Hypoxia; Maternal-Fetal Exchange; Neurophysins; Pregnancy; Sheep; Stress, Physiological; Vasopressins

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Bradycardia; Coronary Circulation; Dextrans; Electrocardiography; Erythrocyte Aggregation; Glucosyltransferases; Glycogen; Heart; Hypoxia; Microcirculation; Mitochondria, Muscle; Myocardium; Oxidative Phosphorylation; Phosphocreatine; Rabbits; Rats; Vasopressins

Topics: Adult; Altitude; Blood Urea Nitrogen; Body Weight; Carbon Dioxide; Dehydration; Diuresis; Furosemide; Heart Rate; Hematocrit; Hemoglobinometry; Humans; Hypoxia; Male; Oxygen; Partial Pressure; Plasma Volume; Time Factors; Vasopressins; Water

Topics: Animals; Anura; Biological Transport, Active; Electric Conductivity; Electric Stimulation; Electrophysiology; Hypoxia; Membrane Potentials; Ouabain; Sodium; Urinary Bladder; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Female; Hypertension, Renal; Hypoxia; Kidney; Nephrectomy; Norepinephrine; Rats; Renin; Ureteral Obstruction; Vasopressins

Topics: Animals; Blood Flow Velocity; Blood Pressure; Cardiac Output; Dogs; Felypressin; Hemorrhage; Hypoxia; Mesenteric Arteries; Mesenteric Veins; Portal Vein; Vasopressins

Topics: Angina Pectoris; Animals; Coronary Vessels; Electrocardiography; Hypoxia; Isoproterenol; Male; Methods; Rabbits; Sympatholytics; Vasodilator Agents; Vasopressins

Topics: Animals; Arteriosclerosis; Cholesterol; Coronary Disease; Coronary Vessels; Epinephrine; Ethanol; Exercise Test; Hypoxia; Isoproterenol; Male; Norepinephrine; Rabbits; Vasopressins

1. An investigation has been carried out into various factors which influence the transmucosal potential difference (p.d.) of rat colon in vivo when the p.d. is either high (> 30 mV) or low (< 20 mV).2. The p.d. was uninfluenced by short duration anaesthesia with ether or pentobarbitone. When anaesthesia was prolonged for several hours, p.d. rose steadily. The gradient of p.d. along the descending colon which developed and its elimination by adrenalectomy suggested that the rise was due to increased secretion of adrenal steroids.3. P.d. was increased by Na depletion after a delay of about 18 hr and fell again following Na repletion with a similar time delay. A characteristic gradient of p.d. along the descending colon was seen.4. Both haemorrhage and anoxia caused a rapid fall of p.d. P.d. was restored rapidly to its previous level when anoxia was corrected.5. Vasopressin (I.V.) in low dose was without effect; in high dose it caused a transient fall of p.d. associated with intense vasoconstriction of gut blood vessels.6. The following factors studied were without effect on p.d.: presence of glucose within the lumen; considerable osmotic gradients across the mucosa; variation of luminal pH over the range 5.2-9.8; intravenous administration of acetazolamide, chlorothiazide, frusemide, triamterene, ethacrynic acid or ouabain. Ouabain in the luminal solution also had no effect in all but two rats in which a small fall of p.d. was seen.7. 2,4-dinitrophenol, 10(-2)M, in the lumen caused a small fall of p.d. only if the p.d. was high.8. Experiments were done to determine the effect on p.d. of altering the ionic composition of the luminal solution. When the p.d. was low (< 20 mV) alteration of [Na], [K] or [Cl] produced small absolute changes of the p.d., all of comparable magnitude. The changes could be interpreted as due to diffusion potentials resulting from the ionic gradients across the mucosa. When the p.d. was high (> 30 mV), it showed a striking dependence on the luminal [Na] only, consistent with the presence of a large p.d. due to active Na transport.

Topics: Acetazolamide; Adrenalectomy; Animals; Biological Transport, Active; Blood Vessels; Chlorides; Chlorothiazide; Colon; Dinitrophenols; Electric Conductivity; Electrophysiology; Ethacrynic Acid; Ethyl Ethers; Furosemide; Glucose; Hemorrhage; Hydrogen-Ion Concentration; Hypoxia; Intestinal Mucosa; Ions; Male; Osmosis; Ouabain; Pentobarbital; Potassium; Rats; Sodium; Triamterene; Vasopressins

Topics: Acidosis; Animals; Blood Pressure; Cardiac Output; Dogs; Female; Heart; Hydrogen-Ion Concentration; Hypoxia; Isoproterenol; Male; Norepinephrine; Sympathomimetics; Vasopressins

Topics: Animals; Blood Pressure; Blood Pressure Determination; Bradycardia; Cardiac Output; Cardiovascular System; Dogs; Heart; Heart Rate; Hemodynamics; Hypoxia; Injections, Intravenous; Lactates; Myocardium; Oxygen; Oxygen Consumption; Respiration; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

Topics: Animals; Electric Stimulation; Ganglia, Autonomic; Glucagon; Glycogen; Hexoses; Histocytochemistry; Hydrocortisone; Hypoxia; Insulin; Microscopy, Electron; Neurons; Oxytocin; Rats; Vasopressins

Topics: Acidosis, Respiratory; Animals; Blood Pressure; Cardiac Output; Dogs; Female; Hypoxia; Isoproterenol; Male; Norepinephrine; Vasopressins

Topics: Animals; Drug Synergism; Electrocardiography; Heart; Hypoxia; Ischemia; Isoproterenol; Male; Rats; Vasopressins

Topics: Acetylcholine; Angiotensin II; Animals; Blood Pressure; Dogs; Hypoxia; Isoproterenol; Norepinephrine; Vasomotor System; Vasopressins

Topics: Adrenal Glands; Anesthesia, General; Blood Volume; Humans; Hypoxia; Kidney; Pituitary-Adrenal System; Surgical Procedures, Operative; Vasopressins

Topics: Acetylcholine; Animals; Blood Flow Velocity; Blood Pressure; Bradykinin; Coronary Vessels; Dogs; Femoral Artery; Heart Rate; Hypoxia; Vasopressins

Topics: Acetylcholine; Animals; Calcium; Carbachol; Cocaine; Cold Temperature; Colon; Guinea Pigs; Hexamethonium Compounds; Histamine; Hypoxia; In Vitro Techniques; Mecamylamine; Morphine; Muscle Contraction; Nicotine; Pentolinium Tartrate; Procaine; Scopolamine; Serotonin; Tetraethylammonium Compounds; Vasopressins

Topics: Animals; Arginine Vasopressin; Biological Transport; Biological Transport, Active; Bombyx; Chlorthalidone; Cholinesterase Inhibitors; Dinitrophenols; Epinephrine; Hypoxia; Intestinal Absorption; Iodoacetates; Ion Transport; Ouabain; Oxytocin; Pharmacology; Potassium; Research; Sodium; Sulfides; Sulfonamides; Vasopressins

Topics: Blood Circulation; Blood Pressure; Carbon Dioxide; Coronary Vessels; Epinephrine; Humans; Hypercapnia; Hypoxia; Norepinephrine; Oxygen; Regional Blood Flow; Vasopressins

Topics: Acetylcholine; Adaptation, Physiological; Animals; Birds; Blood Circulation; Coronary Vessels; Dibenzylchlorethamine; Epinephrine; Hexamethonium Compounds; Hyperemia; Hypoxia; Isoproterenol; Norepinephrine; Oxytocin; Vasopressins

Topics: Blood Pressure; Bradycardia; Cats; Heart Conduction System; Hypoxia; Physiology; Research; Spinal Cord Compression; Vasopressins

Topics: Arginine Vasopressin; Catecholamines; Coronary Disease; Guanethidine; Hypoxia; Metabolism; Norepinephrine; Pharmacology; Phenelzine; Pituitary Hormones, Posterior; Rats; Research; Reserpine; Vasopressins

Synthetic oxytocin (Syntocinon) can be shown to reduce or abolish ST-T changes induced experimentally by hypoxaemia alone, by hypoxaemia and ergometrine, by vasopressin, and by a new procedure involving injection of small doses of picrotoxin into the lateral cerebral ventricle. Ventricular fibrillation induced by picrotoxin can also be reversed by oxytocin. These effects suggest a probable metabolic action of oxytocin against cardiac anoxic changes, and its possible therapeutic usefulness as an antagonist of myocardial ischaemia. It is speculated that this might be a physiological action of the hormone.

Topics: Animals; Arginine Vasopressin; Electrocardiography; Ergonovine; Hypoxia; Myocardial Ischemia; Oxytocics; Oxytocin; Rabbits; Vasopressins