pituitrin and Hypotension

The use of arginine vasopressin (AVP) and terlipressin to treat hypotension in preterm neonates is increasing. Our aim was to review the available evidence on the efficacy and safety of AVP and terlipressin for use in preterm neonates.. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar from inception to September 2021 were searched for studies of AVP and terlipressin in the treatment of hypotension of any cause in preterm neonates. Primary outcomes were improvement in end-organ perfusion and mortality. The risk of bias assessment and certainty of the evidence were performed using appropriate tools.. Fifteen studies describing the use of AVP (n = 12) or terlipressin (n = 3) among 148 preterm neonates were included. Certainly, the available evidence for the primary outcome of end-organ perfusion rated as very low. AVP or terlipressin were used to treat 144 and 4 neonates, respectively. Improvement in markers of end-organ perfusion was reported in 143 (99%) neonates treated with AVP and 3 (75%) treated with terlipressin. The mortality rate was 41% (n = 59) and 50% (n = 2) for neonates who received AVP and terlipressin, respectively. Hyponatremia was the most frequently reported adverse event (n = 37, 25%).. AVP and terlipressin may improve measured blood pressure values and possibly end-organ perfusion among neonates with refractory hypotension. However, the efficacy-safety balance of these drugs should be assessed on an individual basis and as per the underlying cause. Studies on the optimal dosing, efficacy, and safety of AVP and terlipressin in preterm neonates with variable underlying conditions are critically needed.

Topics: Arginine Vasopressin; Humans; Hypotension; Infant, Newborn; Lypressin; Terlipressin; Vasoconstrictor Agents; Vasopressins

Vasodilatory shock is a serious medical condition that increases the morbidity and mortality of perioperative and critically ill patients. Norepinephrine is an established first-line therapy for this condition, but at high doses, it may lead to diminishing returns. Oftentimes, secondary noncatecholamine agents are required in those whose hypotension persists. Angiotensin II and vasopressin are both noncatecholamine agents available for the treatment of hypotension in vasodilatory shock. They have distinct modes of action and unique pharmacologic properties when compared to norepinephrine. Angiotensin II and vasopressin have shown promise in certain subsets of the population, such as those with acute kidney injury, high Acute Physiology and Chronic Health Evaluation II scores, or those receiving cardiac surgery. Any benefit from these drugs must be weighed against the risks, as overall mortality has not been shown to decrease mortality in the general population. The aims of this narrative review are to provide insight into the historical use of noncatecholamine vasopressors and to compare and contrast their unique modes of action, physiologic rationale for administration, efficacy, and safety profiles.

Topics: Angiotensin II; Catecholamines; Humans; Hypotension; Shock, Septic; Vasoconstrictor Agents; Vasodilation; Vasopressins

Primary function of cardiovascular system is to meet body's metabolic demands. The aim of inotrope therapy is to minimise adverse impact of cardiovascular compromise. Current use of inotropes is primarily guided by the pathophysiology of cardiovascular compromise and anticipated actions of inotropes. Lack of significant reduction in morbidity and mortality associated with cardiovascular compromise despite inotrope use, highlights major gaps in our understanding of circulatory targets, thresholds and choices of inotrope therapy. Thus far, prevention of cardiovascular compromise remains the most effective strategy to optimize outcomes. Studies of alternative design are needed for further advancement in cardiovascular therapy in neonates.

Topics: Cardiac Output; Cardiotonic Agents; Dobutamine; Dopamine; Echocardiography; Epinephrine; Heart; Humans; Hypotension; Infant, Newborn; Lactic Acid; Milrinone; Norepinephrine; Perfusion Index; Skin; Spectroscopy, Near-Infrared; Ultrasonography; Urination; Vasopressins

The impact of vasopressin and norepinephrine discontinuation order in the recovery phase of septic shock remains controversial. This systematic review and patient-level meta-analysis were performed to determine the impact of vasopressin and norepinephrine discontinuation order on clinically significant outcomes in the recovery phase of septic shock.. Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, and ClinicalTrials.gov were searched from inception through November 2018 for studies comparing outcomes after the discontinuation of vasopressin or norepinephrine in septic shock. Individual patient-level data were obtained from included studies and combined using a two-stage meta-analysis.. Six studies of low or moderate risk of bias with 957 patients were included. Clinically significant hypotension occurred more frequently when vasopressin was discontinued first compared to norepinephrine (60.7% versus 43.3%, respectively). First discontinuation of norepinephrine compared to vasopressin had lower pooled odds of developing clinically significant hypotension (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07-0.68, I. Discontinuation of norepinephrine prior to vasopressin during the recovery phase of septic shock resulted in less clinically significant hypotension but no difference in mortality or lengths of stay. Larger, prospective studies evaluating the impact of relative vasopressin deficiency and norepinephrine and vasopressin discontinuation order and timing on patient-centered outcomes are needed.

Topics: Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypotension; Incidence; Norepinephrine; Shock, Septic; Vasopressins

There is a distinct lack of age-appropriate cardiotonic drugs, and adult derived formulations continue to be administered, without evidence-based knowledge on their dosing, safety, efficacy, and long-term effects. Dopamine remains the most commonly studied and prescribed cardiotonic drug in the neonatal intensive care unit (NICU), but evidence of its effect on endorgan perfusion still remains. Unlike adult and pediatric critical care, there are significant gaps in our knowledge on the use of various cardiotonic drugs in various forms of circulatory failure in the NICU.

Topics: Adrenal Cortex Hormones; Asphyxia Neonatorum; Cardiotonic Agents; Dobutamine; Dopamine; Heart Defects, Congenital; Humans; Hypotension; Infant, Newborn; Intensive Care Units, Neonatal; Milrinone; Neonatal Sepsis; Norepinephrine; Persistent Fetal Circulation Syndrome; Shock; Simendan; Vasoconstrictor Agents; Vasopressins

To summarize the results of randomized controlled trials on the use of vasopressin as a vasopressor agent in cardiac surgery.. Meta-analysis.. Six-hundred-twenty-five adult patients undergoing elective or emergency cardiac surgery.. Arginine vasopressin infusion (n = 313) or control/standard therapy (n = 312).. The rates of perioperative complications and postoperative mortality were used as primary and secondary endpoints, respectively. Fixed and/or random effects models were used to compare pooled odds ratios. Arginine vasopressin reduced the pooled odds ratio (OR) of perioperative complications (OR, 0.33; 95% confidence interval [CI], 0.2-0.54; p < 0.0001). A sensitivity analysis excluding the largest trial showed an unchanged reduction in perioperative complications (OR, 0.35; 95% CI, 0.18-0.69; p = 0.002). When analyzing each perioperative complication separately, vasopressin reduced the pooled OR of vasodilatory shock (OR, 0.4; 95% CI, 0.16-0.97; p = 0.04) and new-onset atrial fibrillation (OR, 0.42; 95% CI, 0.21-0.82; p = 0.01). The pooled OR of postoperative death was not different between patients treated with arginine vasopressin and those receiving standard therapy or placebo (OR, 0.83; 95% CI, 0.45-1.53; p = 0.55). The funnel plot for the primary endpoint suggested a relevant publication bias. All included trials suffered from a high risk of bias.. Our meta-analysis suggests that arginine vasopressin may reduce the rate of perioperative complications in patients undergoing elective or emergency cardiac surgery. No difference in postoperative mortality was observed. An adequately powered multicenter trial is required for reliable estimation of the effects of arginine vasopressin on perioperative complication rates and mortality in cardiac surgical patients.

Topics: Blood Pressure; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Humans; Hypotension; Infusions, Intravenous; Postoperative Complications; Randomized Controlled Trials as Topic; Vasoconstrictor Agents; Vasopressins

Homeostatic regulation of plasma osmolality (POsm) is critical for normal cellular function in humans. Arginine vasopressin (AVP) is the major hormone responsible for the maintenance of POsm and acts to promote renal water retention in conditions of increased POsm. However, AVP also exerts pressor effects, and its release can be stimulated by the development of effective arterial blood volume depletion. Patients with end-stage renal disease on hemodialysis, particularly those with minimal or no residual renal function, have impaired ability to regulate water retention in response to AVP. While hemodialysis can assist with this task, patients are subject to relatively rapid shifts in volume and electrolytes during the procedure. This can result in the development of transient osmotic gradients that lead to the movement of water from the extracellular to the intracellular space. Hypotension may result-both as a consequence of water movement out of the intravascular compartment, but also from impaired AVP release and inadequate vascular tone. In this review, we explore the evidence for POsm changes during hemodialysis, associations with adverse outcomes, and methods to minimize the rapidity of changes in POsm in an effort to reduce patient symptoms and minimize intra-dialytic hypotension.

Topics: Blood Pressure; Hemodialysis Solutions; Humans; Hypotension; Kidney Failure, Chronic; Neurophysins; Osmolar Concentration; Protein Precursors; Renal Dialysis; Vasopressins; Water-Electrolyte Balance

Arginine vasopressin (AVP) is a common second-line or third-line vasopressor used in critically ill neurosurgical patients. Neurosurgical indications include hyperdynamic therapy for vasospasm, maintenance of cerebral perfusion pressure in patients with intracranial hypertension, and prevention of hypotension in patients with sepsis.. A series of 6 neurosurgical patients receiving AVP infusions developed severe but transient diabetes insipidus (tDI) after cessation of AVP. To our knowledge, no previous reports of this phenomenon in neurosurgical patients have been published. We reviewed the clinical histories, intensive care unit treatment, medication administration records, and laboratory values of these patients, and we found recurrent elevated serum sodium and urine output and decreased urine specific gravity after discontinuation of AVP. Resolution of tDI occurred upon resumption of AVP or administration of desmopressin. Elevated serum sodium levels were often severe, resulting in worsened clinical outcomes. When AVP was resumed, tDI typically recurred if AVP was again tapered and discontinued. Routine administration of desmopressin was useful in controlling sodium levels until the tDI resolved.. Recognition of this phenomenon has caused us to change our clinical management of neurosurgical patients receiving AVP. We hypothesize that tDI is caused by downregulation of the V2 receptor mass in the renal distal convoluted tubule and collecting duct cells. When AVP is discontinued, patients develop nephrogenic tDI secondary to decreased V2 receptor binding, which explains why desmopressin is effective in correcting tDI. Future research includes a large prospective study to determine risk factors for tDI, its incidence, and its pathophysiology.

Topics: Adult; Critical Care; Diabetes Insipidus; Drug Administration Schedule; Female; Humans; Hypotension; Male; Middle Aged; Neurosurgical Procedures; Treatment Outcome; Vasoconstrictor Agents; Vasopressins; Young Adult

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

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

Neonatal hypotension that is refractory to volume expansion, catecholamines, or corticosteroids has a mortality of about 50%. Optimization of blood pressure and tissue perfusion in refractory hypotension may be crucial to improve clinical outcomes. Vasopressin, a neuropeptide hormone, or its analogue terlipressin has been used to treat refractory hypotension in neonates and may be effective.. Our primary objective was to evaluate the efficacy and safety of vasopressin and its synthetic analogues (e.g. terlipressin) in decreasing mortality and adverse neurodevelopmental outcomes, and improving survival in neonates with refractory hypotension. Our secondary objectives were to determine the effects of vasopressin and its analogues (terlipressin) on improvement in blood pressure, increase in urine output, decrease in inotrope score, necrotizing enterocolitis (NEC), periventricular leukomalacia, intraventricular hemorrhage, chronic lung disease, and retinopathy of prematurity (ROP) in neonates with refractory hypotension.. We searched the literature in January 2012, using the search strategy recommended by the Cochrane Neonatal Group. We searched electronic databases (CENTRAL (The Cochrane Library), MEDLINE, CINAHL, EMBASE), abstracts of the Pediatric Academic Societies, web sites for registered trials at www.clinicaltrials.gov and www.controlled-trials.com and in the reference list of identified articles.. Randomized or quasi-randomized trials evaluating vasopressin or its analogues, at any dosage or duration used as an adjunct to standard therapy (any combination of volume expansion, inotropic agents and corticosteroids) to treat refractory hypotension in neonates.. We followed the standard methods of The Cochrane Collaboration for conducting a systematic review. Two review authors (BS and MP) independently assessed the titles and abstracts of studies identified by the search strategy for eligibility for inclusion. We obtained the full text version if eligibility could not be done reliably by title and abstract. We resolved any differences by mutual discussion. We designed electronic forms for trial inclusion/exclusion, data extraction, and for requesting additional published information from authors of the original reports.. Our search did not identify any completed or ongoing trials that met our inclusion criteria. Three studies that did not include neonates and one study where the objective was not to treat neonates with refractory hypotension were excluded.. There is insufficient evidence to recommend or refute the use of vasopressin or its analogues in the treatment of refractory hypotension in neonates. Well-designed, adequately powered, randomized controlled studies are necessary to address efficacy, optimal dosing, safety and long-term neurodevelopmental and pulmonary outcomes. 

Topics: Humans; Hypotension; Infant, Newborn; Lypressin; Terlipressin; Vasoconstrictor Agents; Vasopressins

Uncontrolled elevation in plasma potassium within minutes of rapid blood volume loss is associated with mortality and distinguishes nonsurvivors of severe hemorrhage from survivors. In a pig model of severe hemorrhage, we discovered that along with a sharp increase in plasma potassium coincident with a shut down of urine flow, nonsurvivors also had an insufficient vasopressin response to hemorrhage. In contrast, survivors did have elevated vasopressin levels in response to hemorrhage and maintained plasma potassium within normal limits. While it has been demonstrated for some time that vasopressin can influence secretion of potassium in the distal nephron, the magnitude of this effect and conditions under which this contributes to physiological modulation of potassium excretion has yet to be defined. In this review, we assess the evidence that would suggest that vasopressin plays a key role in modulating potassium excretion and is important in the regulation of potassium homeostasis during hemorrhage.

Topics: Animals; Hemorrhage; Homeostasis; Hypotension; Potassium; Swine; Vasopressins

Sufficient organ blood flow of healthy newborn babies is maintained by relatively low systemic blood pressure. Premature infants are at an increased risk of systemic hypotension, often but not obviously, resulting in hypoperfusion of the cerebral, renal and intestinal vascular beds. Maintaining a stable blood pressure in preterm babies is of high importance in order to prevent complications such as intraventricular hemorrhage, periventricular leucomalatia, necrotizing enterocolitis or renal failure. The regulation of systemic and local hemodynamics in newborns differs substantially from that of the adults. Developmental changes in catecholamine sensitivity, higher local vasodilator factor activity and structural differences of the immature myocardium should be taken into account when applying vasoactive agents in neonates. The effects of widely used catecholamines such as dopamine, epinephrine or dobutamine can not be directly adapted from adult therapeutics to neonatal care. Their administration should be supported by data on their effects on systemic and cerebral blood flow in addition to blood pressure changes. At the bedside, neonatologists should use new diagnostic tools to differentiate between neonatal hypotension and hypoperfusion, vasoconstriction and myocardial dysfunction in order to choose the appropriate medication. Newer vasoactive agents already used in adult or pediatric cardiovascular therapy such as milrinone, levosimendan or terlipressin need to be carefully evaluated before introducing them to the treatment of neonatal hypotensive states. Well-designed preclinical and human newborn studies also evaluating their local effects are warranted.

Topics: Adrenal Cortex Hormones; Cardiovascular System; Catecholamines; Humans; Hydrazones; Hypotension; Infant, Newborn; Milrinone; Pyridazines; Simendan; Vasodilator Agents; Vasopressins

The use of norepinephrine, and probably vasopressor therapy in general, in intensive care patients with hypotensive vasodilatation despite fluid resuscitation and evidence of acute kidney injury remains the subject of much debate and controversy. Although there is concern about the use of these drugs, these concerns are unfounded. At this time, the experimental and human data strongly suggest that, in these patients, vasopressor therapy is safe and probably beneficial from a renal, and probably general, point of view. On the basis of currently available evidence, in hypotensive vasodilated patients with acute kidney injury, restoration of blood pressure within autoregulatory values should occur promptly with noradrenaline and be sustained until such vasodilatation dissipates. The additional role of other vasopressors in these situations remains unclear. The addition of vasopressin may be helpful in individual patients, but widespread use is not supported by evidence. Alpha-dose dopamine has no advantages over noradrenaline and is not as reliably effective in restoring blood pressure and urine output. Its widespread use cannot be supported in patients with vasodilatation and acute kidney injury. Other vasopressor drugs such as epinephrine and phenylephrine may be similar in efficacy to noradrenaline. However, experience and available data with their use is vastly less than with noradrenaline. Adrenaline, in addition, is associated with hyperglycemia, hyperlactatemia, acidosis, and hypokalemia. Terlipressin appears useful in patients with acute kidney injury secondary to hepatorenal syndrome. Whether it is superior to noradrenaline in this setting remains uncertain, and more studies are needed before recommendations can be made.

Topics: Acute Kidney Injury; Animals; Blood Pressure; Critical Care; Glomerular Filtration Rate; Humans; Hypotension; Norepinephrine; Renal Circulation; Vasoconstrictor Agents; Vasopressins

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

Clinical reports and experimental studies support the beneficial effects of low-dose vasopressin infusions in vasodilatory shock. Before we can recommend vasopressin for routine clinical use in vasodilatory shock, and particularly septic shock, we must await the results of currently ongoing and recently completed randomized clinical trials to ensure that vasopressin does indeed have beneficial effects on organ function and outcome.

Topics: Animals; Humans; Hypotension; Randomized Controlled Trials as Topic; Renal Circulation; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Intervention for cardiac arrest may require intervention for electrical abnormalities or hemodynamic instability. These actions can result in ineffective cardiac functioning and systemic hypotension. Vasopressors are capable of improving severe hypotension that can result from reduced cardiovascular contractility or heart rate. These vasopressor actions are critical to successful resuscitation efforts for patients.

Topics: Cardiopulmonary Resuscitation; Dobutamine; Dopamine; Epinephrine; Heart Arrest; Heart Rate; Humans; Hypotension; Myocardial Contraction; Norepinephrine; Nurse's Role; Receptors, Adrenergic; Severity of Illness Index; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

The widespread physiologic changes that follow brain stem death lead to a high incidence of complications in the donor and jeopardize vital organ function. Strategies for the management of organ donors exist whereby the rapid physiologic decline seen after brain stem death can be stabilized by active donor resuscitation so that the functional integrity of potentially transplantable organs is maintained. Understanding the complex physiologic changes that occur after brain stem death is crucial to the development of effective donor management strategies. This article reviews the pathophysiologic changes that occur after brain stem death and discusses controversies in donor management.

Topics: Brain Death; Brain Stem; Diabetes Insipidus; Disseminated Intravascular Coagulation; Endocrine System; Hormones; Humans; Hypotension; Insulin; Lung; Thyroid Gland; Tissue Donors; Vasopressins

Osmotic and hemodynamic stress are the two primary regulators of vasopressin (VP) release from the posterior pituitary. The pathways providing information about plasma osmolality and blood pressure or blood volume are distinct and utilize different chemical neurotransmitters. Osmotic regulation of VP release is dependent upon afferents from the lamina terminalis region. Glutamate is an important transmitter in this system and angiotensinergic afferents from this region to the VP neurons modulate responses to osmotic challenges. Hemodynamic information is transmitted to the VP neurons via multisynaptic pathways from the brainstem with the A1 catecholamine neurons of the ventrolateral medulla providing the final link for information about decreases in blood pressure and volume. Several neurotransmitters and neuropeptides are expressed in the A1 neurons including norepinephrine (NE), ATP, neuropeptide Y, and substance P. The impact of co-release of these agents on VP release is reviewed and the potential physiological significance is discussed.

Topics: Animals; Blood; Humans; Hypotension; Hypovolemia; Neurotransmitter Agents; Vasopressins; Water-Electrolyte Balance

Osmotic demyelination of the brain (ODS) is a dreaded complication that typically occurs several days after aggressive therapy for chronic hyponatraemia, but is eminently avoidable. In this teaching exercise, Professor McCance, an imaginary consultant, is asked to explain how he would have treated a 28-year-old female who had hyperkalaemia, hypoglycaemia, hypotension and hyponatraemia (118 mM) to prevent the development of ODS. He begins with a review of the physiology, including his own landmark work on chronic hyponatraemia associated with a contracted extracellular fluid volume. Adding quantitative analysis, the cause of the excessive rise in plasma sodium concentration is revealed, and a better plan for therapy is proposed.

Topics: Addison Disease; Adult; Brain Diseases; Demyelinating Diseases; Female; Humans; Hyperkalemia; Hypoglycemia; Hyponatremia; Hypotension; Renal Agents; Syndrome; Vasopressins; Water-Electrolyte Imbalance

Topics: Animals; Humans; Hypotension; Muscle, Smooth, Vascular; Nitric Oxide; Potassium Channels; Shock; Vasoconstriction; Vasodilation; Vasopressins

Topics: Baroreflex; Blood Volume; Cerebrovascular Circulation; Epinephrine; Heart Ventricles; Humans; Hypotension; Mechanoreceptors; Pressoreceptors; Renin; Serotonin; Syncope, Vasovagal; Vasodilation; Vasopressins

Topics: Humans; Hypotension; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Topics: Animals; Cattle; Endocrine Glands; Humans; Hypotension; Hypothalamus; Neurophysins; Oxytocin; Rats; Shock; Stress, Physiological; Vasopressins

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

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

Topics: Acetylcholine; Acute Kidney Injury; Angiotensin II; Animals; Bradykinin; Diuretics; Dogs; Dopamine; Electric Stimulation; Epinephrine; Heart Failure; Hemorrhage; Humans; Hypotension; Isoproterenol; Kidney Cortex; Kidney Transplantation; Liver Cirrhosis; Norepinephrine; Oxytocin; Prostaglandins; Regional Blood Flow; Transplantation, Homologous; Ureter; Vasomotor System; Vasopressins; Vena Cava, Inferior; Water-Electrolyte Balance

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

Topics: Adult; Clinical Protocols; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Hypotension; Infusions, Intravenous; Male; Receptors, Vasopressin; Research Design; Risk Assessment; Shock, Septic; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V. This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng/kg/minute (n = 19), 3.75 ng/kg/minute (n = 2), or placebo (n = 21) until shock resolution or a maximum of 7 days. If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added. Co-primary endpoints were maintenance of MAP >60 mmHg without norepinephrine, norepinephrine dose, and proportion of patients maintaining MAP >60 mmHg with or without norepinephrine over 7 days. Secondary endpoints included cumulative fluid balance, organ dysfunction, pharmacokinetics, and safety.. A higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01). The 7-day cumulative doses of norepinephrine were 761, 659, and 249 μg/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01). Norepinephrine infusion was weaned more rapidly in selepressin 2.5 ng/kg/minute vs. placebo (0.04 vs. 0.18 μg/kg/minute at 24 h, p < 0.001), successfully maintaining target MAP and reducing norepinephrine dose vs. placebo (first 24 h, p < 0.001). Cumulative net fluid balance was lower from day 5 onward in the selepressin 2.5 ng/kg/minute group vs. placebo (p < 0.05). The selepressin 2.5 ng/kg/minute group had a greater proportion of days alive and free of ventilation vs. placebo (p < 0.02). Selepressin (2.5 ng/kg/minute) was well tolerated, with a similar frequency of treatment-emergent adverse events for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group.. In septic shock patients, selepressin 2.5 ng/kg/minute was able to rapidly replace norepinephrine while maintaining adequate MAP, and it may improve fluid balance and shorten the time of mechanical ventilation.. ClinicalTrials.gov, NCT01000649 . Registered on September 30, 2009.

Topics: Adolescent; Adult; Aged; Belgium; Child; Denmark; Double-Blind Method; Female; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Placebos; Receptors, Vasopressin; Shock, Septic; United States; Vasoconstrictor Agents; Vasopressins

To evaluate vasopressin vs dopamine as initial therapy in extremely low birth weight (ELBW) infants with hypotension during the first 24 hours of life.. ELBW infants with hypertension ≤ 30 weeks' gestation and ≤ 24 hours old randomly received treatment with vasopressin or dopamine in a blinded fashion. Normotensive infants not receiving vasopressor support served as a comparison group.. Twenty ELBW infants with hypertension received vasopressin (n = 10) or dopamine (n = 10), and 50 were enrolled for comparison. Mean gestational age was 25.6 ± 1.4 weeks and birth weight 705 ± 154 g. Response to vasopressin paralleled that of dopamine in time to adequate mean blood pressure (Kaplan-Meier curve, P = .986); 90% of infants in each treatment group responded with adequate blood pressure. The vasopressin group received fewer doses of surfactant (P < .05), had lower PaCO2 values (P < .05), and were not tachycardic (P < .001) during vasopressin administration, compared with the dopamine group.. Vasopressin in ELBW infants as the initial agent for early hypotension appeared safe. This pilot study supports a larger randomized controlled trial of vasopressin vs dopamine therapy in ELBW infants with hypotension.

Topics: Blood Pressure; Cardiotonic Agents; Dopamine; Dose-Response Relationship, Drug; Double-Blind Method; Feasibility Studies; Female; Follow-Up Studies; Gestational Age; Humans; Hypotension; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infusions, Intravenous; Male; Pilot Projects; Prospective Studies; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Vasoconstrictors such as norepinephrine and vasopressin are commonly used to raise the blood pressure during myocardial revascularization. The internal thoracic artery is commonly used for coronary artery grafting because of its long-term patency. However, the internal thoracic artery is a living conduit that responds to vasoactive substances. The objective of this study was to measure change in internal thoracic arterial flow after infusion of norepinephrine or vasopressin.. Forty-one patients undergoing elective off-pump coronary artery bypass grafting participated in this study. After the median sternotomy, the left internal thoracic artery was dissected with a pedicle and grafted to the left anterior descending artery. After all anastomoses were performed and hemodynamic parameters were stable, the grafted internal thoracic arterial blood flow was measured by transit time flowmeter on the distal portion of the graft as a baseline. Norepinephrine or vasopressin was then infused until mean arterial pressure was increased to 20% of baseline. Graft flow and hemodynamic variables were measured when mean arterial pressure reached the intended level.. Baseline grafted internal thoracic arterial flows were similar (norepinephrine 57.1 ± 17.7 mL min(-1), vasopressin 66.0 ± 34.3 mL min(-1)). With norepinephrine, flow increased significantly relative to baseline (77.2 ± 31.0 mL min(-1)); with vasopressin, it remained unchanged (68.3 ± 37.0 mL min(-1)).. For patients needing vasopressor support after coronary artery bypass grafting, norepinephrine appeared superior to vasopressin because of increased internal thoracic arterial flow.

Topics: Aged; Blood Flow Velocity; Blood Pressure; Coronary Artery Bypass, Off-Pump; Coronary Circulation; Elective Surgical Procedures; Female; Humans; Hypotension; Infusions, Parenteral; Korea; Male; Mammary Arteries; Middle Aged; Norepinephrine; Sternotomy; Ultrasonography; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

The purpose of this study was to compare the effects of continuation versus discontinuation of the angiotensin-converting enzyme (ACE) inhibitor ramipril and assess the efficacy of prophylactic vasopressin infusion on hemodynamic stability and vasoactive drug requirements in patients undergoing coronary artery bypass graft (CABG) surgery.. A prospective, randomized, double-blinded, single-center clinical study.. Tertiary care hospital.. Forty-seven patients on the ACE inhibitor ramipril for 6 weeks before undergoing elective primary CABG surgery on cardiopulmonary bypass (CPB).. Patients were randomly divided into 3 groups: group A (n = 16), patients discontinued ramipril 24 hours before surgery; group B (n = 16), patients continued ramipril until the morning of surgery; and group C (n = 15), patients continued ramipril until the morning of surgery and received vasopressin infusion (0.03 U/min) from the onset of rewarming until the hemodynamics were stable without vasopressor agents. The anesthetic technique and conduct of CPB were standardized for all the groups. Hemodynamic parameters and vasoactive drug requirements were recorded for 3 days postoperatively.. Patients in group A maintained stable mean arterial pressure (MAP) and systemic vascular resistance (SVR). In group B, MAP and SVR decreased after the induction of anesthesia and remained so throughout surgery (p < 0.05). In group C, MAP and SVR decreased upon the induction of anesthesia (p < 0.05) but normalized after CPB.. Preoperative ACE inhibitor continuation predisposed to hypotension upon the induction of anesthesia and in the post-CPB period. Prophylactic low-dose vasopressin infusion prevented post-CPB hypotension. Low-dose vasopressin can be considered as potential therapy in these patients.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Artery Bypass; Double-Blind Method; Female; Heart Rate; Humans; Hypotension; Male; Middle Aged; Prospective Studies; Ramipril; Vasopressins

Arginine vasopressin (AVP), an endogenous hormone with vasopressor properties, may be inadequately secreted during episodes of intradialytic hypotension (IDH).. To evaluate this, we performed a prospective, observational pilot study of 20 chronic hemodialysis patients assessing the baseline AVP level and trend of AVP with ultrafiltration in patients with a diagnosis of IDH compared with patients without IDH. Ten symptomatic IDH patients and 10 controls were enrolled and matched for age, gender, and dialysis vintage. AVP levels were obtained hourly throughout the dialysis session and during hypotensive episodes.. We observed that IDH patients experienced greater decreases in both systolic and diastolic blood pressure during the dialysis session despite equivalent ultrafiltration in both groups. AVP concentration did not increase in the IDH patients (5.0 +/- 1.8) compared with controls (6.4 +/- 6.0) (P = 0.5) despite hypotensive events.. This study suggests that symptomatic IDH patients are unable to mount an appropriate increase in AVP secretion in the setting of hypotension. These findings support the possibility of AVP as a mechanism driven therapy for patients with symptomatic IDH.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Case-Control Studies; Diastole; Female; Hemodiafiltration; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Neurophysins; Pilot Projects; Prospective Studies; Protein Precursors; Renal Dialysis; Research Design; Severity of Illness Index; Sodium; Systole; Time Factors; Vasopressins

Phosphodiesterase inhibitor is essential to the pharmacologic management of decompensated heart failure because it increases contractility and decreases afterload of right ventricle. It also improves hemodynamics and increases blood flow of the grafted internal mammary arteries and middle cerebral arteries during coronary artery bypass surgery. However, it induces vasodilation and necessitates the use of vasoconstrictors, such as norepinephrine. We hypothesized that vasopressin could recover hypotension induced by milrinone with less effect on pulmonary vascular resistance (PVR) compared to norepinephrine.. Fifty patients, undergoing coronary artery bypass graft (CABG) surgery, were assigned randomly in a double-blind manner to receive either vasopressin or norepinephrine. After baseline hemodynamic measurements, a loading dose of milrinone 50 microg/kg was infused slowly for 20 min followed by continuous infusion of 0.5 microg/(kg min). Immediately after the loading dose of milrinone, hemodynamic variables were measured, and vasopressin (VP group) or norepinephrine (NE groups) was infused. After being titrated until the mean arterial pressure was increased by 20%, hemodynamic variables were measured again.. Milrinone infusion reduced both systemic vascular resistance (SVR, 1218+/-299 dynes/cm5 vs 838+/-209 dynes/cm5, 1345+/-299 dynes/cm5 vs 1011+/-195 dynes/cm5) and PVR (95+/-34 dynes/cm5 vs 72+/-30 dynes/cm5, 119+/-85 dynes/cm5 vs 87+/-33 dynes/cm5) in the VP and NE groups, respectively. Vasopressin and norepinephrine infusion increased both SVR (838+/-209 dynes/cm5 vs 1100+/-244 dynes/cm5, 1011+/-195 dynes/cm5 vs 1446+/-681 dynes/cm5, respectively) and PVR (72+/-30 dynes/cm5 vs 84+/-18 dynes/cm5, 87+/-33 dynes/cm5 vs 139+/-97 dynes/cm5, respectively). The PRV/SVR ratio was decreased after vasopressin infusion (0.10+/-0.03 vs 0.08+/-0.03), while no changes were found after norepinephrine infusion (0.09+/-0.02 vs 0.09+/-0.02).. In the patients undergoing CABG surgery, both norepinephrine and low dose vasopressin were effective in restoring milrinone-induced decrease of SVR. However, only low-dose vasopressin decreased the PVR/SVR ratio that was increased by milrinone. Considering the importance of maintaining systemic perfusion pressure as well as reducing right heart afterload, milrinone-vasopressin may provide better hemodynamics than milrinone-norephinephrine during the management of right heart failure.

Topics: Aged; Coronary Artery Bypass, Off-Pump; Double-Blind Method; Female; Humans; Hypotension; Intraoperative Care; Intraoperative Complications; Male; Middle Aged; Milrinone; Norepinephrine; Phosphodiesterase Inhibitors; Prospective Studies; Vascular Resistance; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

To determine the effects of dobutamine, norepinephrine, and vasopressin on cardiovascular function and gastric mucosal perfusion in anesthetized foals during isoflurane-induced hypotension.. 6 foals that were 1 to 5 days of age.. 6 foals received 3 vasoactive drugs with at least 24 hours between treatments. Treatments consisted of dobutamine (4 and 8 Sang/kg/min), norepinephrine (0.3 and 1.0 Sang/kg/min), and vasopressin (0.3 and 1.0 mU/kg/min) administered IV. Foals were maintained at a steady hypotensive state induced by a deep level of isoflurane anesthesia for 30 minutes, and baseline cardiorespiratory variables were recorded. Vasoactive drugs were administered at the low infusion rate for 15 minutes, and cardiorespiratory variables were recorded. Drugs were then administered at the high infusion rate for 15 minutes, and cardiorespiratory variables were recorded a third time. Gastric mucosal perfusion was measured by tonometry at the same time points.. Dobutamine and norepinephrine administration improved cardiac index. Vascular resistance was increased by norepinephrine and vasopressin administration but decreased by dobutamine at the high infusion rate. Blood pressure was increased by all treatments but was significantly higher during the high infusion rate of norepinephrine. Oxygen delivery was significantly increased by norepinephrine and dobutamine administration; O2 consumption decreased with dobutamine. The O2 extraction ratio was decreased following norepinephrine and dobutamine treatments. The gastric to arterial CO2 gap was significantly increased during administration of vasopressin at the high infusion rate.. Norepinephrine and dobutamine are better alternatives than vasopressin for restoring cardiovascular function and maintaining splanchnic circulation during isoflurane-induced hypotension in neonatal foals.

Topics: Anesthetics, Inhalation; Animals; Blood Pressure; Dobutamine; Dose-Response Relationship, Drug; Female; Gastric Mucosa; Heart Rate; Horses; Hypotension; Isoflurane; Male; Norepinephrine; Sympathomimetics; Vasoconstrictor Agents; Vasopressins

To study the effect of continuous infusion of vasopressin on the splanchnic circulation in patients with severe septic shock.. Prospective clinical study.. ICU in a teaching hospital.. Eleven consecutive patients with documented septic shock who remained hypotensive despite norepinephrine infusion at a rate > or =0.2 microg/kg/min.. Insertion of a gastric tonometry catheter, and continuous infusion of vasopressin 0.04 U/min during 4 h.. Difference between gastric and arterial CO(2) partial pressure (P[g-a]CO(2) gap), mean arterial pressure, and cardiac index were recorded at baseline and after 15 min, 30 min, 60 min, 120 min, and 240 min.. The median P(g-a)CO(2) gap increased from 5 mm Hg at baseline to 19 mm Hg after 4 h (p = 0.022). Mean arterial pressure increased from 61 +/- 13 mm Hg at baseline to 68 +/- 9 mm Hg after 4 h (p = 0.055). No significant changes in cardiac index were noted.. In norepinephrine-dependent patients in septic shock, continuous infusion of low-dose vasopressin results in a significant increase of the P(g-a)CO(2) gap compatible with GI hypoperfusion.

Topics: Adult; Aged; APACHE; Blood Pressure; Critical Care; Female; Humans; Hypotension; Male; Manometry; Middle Aged; Norepinephrine; Pneumonia; Prospective Studies; Shock, Septic; Splanchnic Circulation; Vasoconstrictor Agents; Vasopressins

This study was conducted prospectively to compare the effect of epidural fentanyl (EP-F), epidural lidocaine (EP-L), and intravenous fentanyl (IV-F) on hemodynamic and hormonal responses to surgery and postoperative analgesic requirement in 30 patients undergoing gastrectomy during isoflurane anesthesia. An epidural catheter was placed via the T8-9 interspace. Group EP-F received fentanyl 2 micrograms/kg in 10 mL saline, and Group EP-L, 10 mL 1.5% lidocaine, epidurally; Group IV-F was given fentanyl, 2 micrograms/kg, IV. Fifty percent of the original dose was repeated every hour. Hemodynamic data and plasma hormonal levels were compared between those before and those at 1 h after skin incision. The total number of analgesic administrations within the first 48 h postoperatively were compared. Group EP-L developed more frequent episodes of hypotension. Group IV-F required higher isoflurane concentrations and the plasma epinephrine levels increased more than in Groups EP-F and EP-L. In Groups EP-L and IV-F, the plasma antidiuretic hormone (ADH) level increased more than in Group EP-F. In Groups EP-F and IV-F, the plasma cortisol and adrenocorticotropic hormone (ACTH) levels increased more than in Group EP-L. The use of postoperative analgesics was significantly less in Group EP-F. In conclusion, in Group EP-F, attenuated hormonal responses to surgery was accompanied with less hypotension and postoperative analgesic requirements were reduced.

Topics: Adjuvants, Anesthesia; Adrenocorticotropic Hormone; Adult; Aged; Analgesics; Anesthesia, Epidural; Anesthesia, Inhalation; Anesthetics, Inhalation; Anesthetics, Intravenous; Anesthetics, Local; Epinephrine; Female; Fentanyl; Gastrectomy; Hemodynamics; Hormones; Humans; Hydrocortisone; Hypotension; Isoflurane; Lidocaine; Male; Middle Aged; Pain, Postoperative; Prospective Studies; Vasopressins

To determine whether or not the blockade of sympathetic efferents by epidural anaesthesia blunts the normal increase in plasma renin activity in response to hypotension, we assessed the effect of hypotensive thoracic epidural anaesthesia with widespread sympathetic blockade on plasma renin activity. Plasma renin activity and vasopressin concentration, arterial pressure, and serum osmolality were measured in 17 patients before and after random epidural injection of either 6.7 ml of 0.75% bupivacaine (n = 7) or the same volume of saline (n = 10). As an indicator for efferent sympathetic drive, skin temperatures were measured on the hand and foot. A decrease in mean arterial pressure by more than 25% of baseline values was prospectively defined as hypotension requiring intervention. Thoracic epidural anaesthesia induced a decrease in mean arterial pressure of 24 mmHg (range 16-47) from 101 mmHg to 77 mmHg (P less than 0.001 vs. saline). Despite hypotension, plasma renin activity remained unchanged [medians 2.9 ng ml-1 h-1 (0-9.1) vs. 3.4 ng ml-1 h-1 (0-13.8)]. In contrast, vasopressin concentrations increased from a median of 3.8 pg ml-1 (0.5-8.2) to 6.0 pg ml-1 (4.2-33.6; P = 0.025). Both hand and foot skin temperatures increased significantly indicating widespread extent of sympathetic blockade. Serum osmolality did not change. With epidural saline, variables remained unchanged. Thus, during hypotension induced by widespread attenuation of efferent sympathetic drive through thoracic epidural anaesthesia, renin activity did not change, whilst vasopressin concentrations increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia, Epidural; Autonomic Nerve Block; Bupivacaine; Female; Humans; Hypotension; Male; Renin; Vasopressins

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

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

Topics: Cohort Studies; Humans; Hypotension; Incidence; Norepinephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Two case reports present the use of vasopressin for treating refractory hypotension associated with continued angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy prior to general anesthesia for oral surgery. Both patients were treated in an ambulatory dental surgery clinic and took either their ACEI or ARB medication for hypertension within 24 hours prior to undergoing an intubated general anesthetic. Persistent profound hypotension was encountered intraoperatively that was refractory to treatment with traditional methods. However, the ACEI- or ARB-induced refractory hypotension was successfully managed with the administration of vasopressin.

Topics: Anesthesia, General; Anesthetics, General; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Dentistry; Humans; Hypotension; Postoperative Complications; Retrospective Studies; Vasopressins

The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order.. The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation.. In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality.. A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed.. The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Topics: Adult; Humans; Hypotension; Norepinephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins; Ventricular Function, Left

Despite its increasing use in neonates, the literature on the use of vasopressin (VP) in neonates is limited. The aim of this study is to evaluate the systemic and pulmonary effects of VP in neonates and to assess its safety among them.. This retrospective study enrolled all neonates in two level III neonatal intensive care units in Winnipeg, Manitoba, who had received VP therapy between 2011 and 2016. Infants with congenital malformations/chromosomal disorders were excluded. The changes in cardiovascular and pulmonary parameters were collected from patient charts. The primary outcome was the mean blood pressure (MBP) post-VP initiation. Secondary outcomes included systolic blood pressure (SBP) and diastolic blood pressure (DBP), vasoactive inotropic score (VIS), pH, urine output, lactate, base deficit (BD), mean airway pressure (MAP), and oxygen requirement.. A total of 33 episodes from 26 neonates were analyzed. The postnatal age at VP initiation was 14 days (interquartile range [IQR]: 4-25), and the median starting dose was 0.3 mU/kg/min (IQR: 0.2-0.5). MBP improved significantly after VP initiation from 28 to 39 mm Hg 24 hours after VP initiation (. VP appears to be a promising rescue therapy in catecholamine resistant shock or refractory pulmonary hypertension in neonates.

Topics: Blood Pressure; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Hypotension; Infant, Newborn; Infant, Newborn, Diseases; Lung; Male; Retrospective Studies; Urine; Vasoconstrictor Agents; Vasopressins

Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor is a counter-regulatory axis that counteracts detrimental renin-angiotensin system (RAS) effects, especially regarding systemic inflammation, vasopressin (AVP) release, and hypothalamic-pituitary-adrenal (HPA) activation. However, it is not completely understood whether this system may control centrally or systemically the late phase of systemic inflammation. Thus, the aim of this study was to determine whether intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation through the activation of humoral pathways in late phase of endotoxemia. Endotoxemia was induced by systemic injection of lipopolysaccharide (LPS) (1.5 mg/kg, i.v.) in Wistar rats. Ang-(1-7) (0.3 nmol in 2 µL) promoted the release of AVP and attenuated interleukin-6 (IL-6) and nitric oxide (NO) levels but increased interleukin-10 (IL-10) in the serum of the endotoxemic rats. The central administration of Mas receptor antagonist A779 (3 nmol in 2 µL, i.c.v.) abolished these anti-inflammatory effects in endotoxemic rats. Furthermore, Ang-(1-7) applied centrally restored mean arterial blood pressure (MABP) without affecting heart rate (HR) and prevented vascular hyporesponsiveness to norepinephrine (NE) and AVP in animals that received LPS. Together, our results indicate that Ang-(1-7) applied centrally promotes a systemic anti-inflammatory effect through the central Mas receptor and activation of the humoral pathway mediated by AVP.

Topics: Angiotensin I; Animals; Endotoxemia; Gene Expression Regulation; Hypotension; Inflammation; Lactic Acid; Lipopolysaccharides; Male; Osmolar Concentration; Peptide Fragments; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats, Wistar; Receptors, G-Protein-Coupled; Sodium; Vasopressins

Angiotensin II (AngII) immunoreactive cells, fibers and receptors, were found in the parvocelluar region of paraventricular nucleus (PVNp) and AngII receptors are present on vasopressinergic neurons. However, the mechanism by which vasopressin (AVP) and AngII may interact to regulate arterial pressure is not known. Thus, we tested the cardiovascular effects of blockade of the AngII receptors on AVP neurons and blockade of vasopressin V1a receptors on AngII neurons. We also explored whether the PVNp vasopressin plays a regulatory role during hypotension in anesthetized rat or not. Hypovolemic-hypotension was induced by gradual bleeding from femoral venous catheter. Either AngII or AVP injected into the PVNp produced pressor and tachycardia responses. The responses to AngII were blocked by V1a receptor antagonist. The responses to AVP were partially attenuated by AT1 antagonist and greatly attenuated by AT2 antagonist. Hemorrhage augmented the pressor response to AVP, indicating that during hemorrhage, sensitivity of PVNp to vasopressin was increased. By hemorrhagic-hypotension and bilateral blockade of V1a receptors of the PVNp, we found that vasopressinergic neurons of the PVNp regulate arterial pressure towards normal during hypotension. Taken together these findings and our previous findings about angII (Khanmoradi and Nasimi, 2017a) for the first time, we found that a mutual cooperative system of angiotensinergic and vasopressinergic neurons in the PVNp is a major regulatory controller of the cardiovascular system during hypotension.

Topics: Angiotensin I; Angiotensin II; Angiotensin II Type 2 Receptor Blockers; Animals; Arterial Pressure; Hemorrhage; Hypotension; Hypovolemia; Male; Nerve Net; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Vasopressins

The optimal order of vasopressor discontinuation during shock resolution remains unclear. We evaluated the incidence of hypotension in patients receiving concomitant vasopressin (VP) and norepinephrine (NE) based on the order of their discontinuation. In this retrospective cohort study, consecutive patients receiving concomitant VP and NE infusions for shock admitted to intensive care units were evaluated. The primary outcome was hypotension incidence following discontinuation of VP or NE (VP1 and NE1 groups, respectively). Secondary outcomes included the incidence of acute kidney injury (AKI) and arrhythmias. Subgroup analysis was conducted by examining outcomes based on the type of shock. Of the 2,035 included patients, 952 (46.8%) were VP1 and 1,083 (53.2%) were NE1. VP1 had a higher incidence of hypotension than NE1 (42.1% vs. 14.2%; P < 0.001), longer time to shock reversal (median: 2.5 vs. 2.2 days; P = .009), higher hospital [29% (278/952) vs. 24% (258/1083); P = .006], and 28-day mortality [37% (348/952) vs. 29% (317/1,083); P < 0.001] when compared with the NE1 group. There were no differences in ICU mortality, ICU and hospital length of stay, new-onset arrhythmia, or AKI incidence between the two groups. In subgroup analyses based on different types of shock, similar outcomes were observed. After adjustments, hypotension in the following 24 h and 28-day mortality were significantly higher in VP1 (Odds ratios (OR) 4.08(3.28, 5.07); p-value < .001 and 1.27(1.04, 1.55); p-value < .001, respectively). Besides, in a multivariable model, the need for renal replacement therapy (OR 1.68 (1.34, 2.12); p-value < .001) was significantly higher in VP1. Among patients with shock who received concomitant VP and NE, the VP1 group was associated with a higher incidence of hypotension in comparison with NE1. Future studies need to validate our findings and their impact on clinical outcomes.

Topics: Aged; Female; Humans; Hypotension; Incidence; Male; Middle Aged; Norepinephrine; Retrospective Studies; Vasoconstrictor Agents; Vasopressins

A 72-year-old man with end-stage renal disease (ESRD) undergoing transurethral resection of a bladder tumor experienced severe and prolonged hypotension after receiving oral 5-aminolevulinic acid (5-ALA). Continuous infusions of norepinephrine and vasopressin ultimately resolved the hypotension over the course of 26 hours. It is uncertain whether 5-ALA is causative or is a contributing factor that influences other factors, such as hypovolemia after hemodialysis and autonomic nerve dysfunction associated with ESRD. Our findings suggest that anesthesiologists should be aware of the possible occurrence of hypotension after administration of 5-ALA, and urologists should consider intravesical 5-ALA administration in patients with ESRD.

Topics: Administration, Oral; Aged; Aminolevulinic Acid; Humans; Hypotension; Kidney Failure, Chronic; Norepinephrine; Treatment Outcome; Urinary Bladder Neoplasms; Urologic Surgical Procedures; Vasopressins

Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes.. This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality.. Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01).. Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.

Topics: Aged; Arterial Pressure; Cost-Benefit Analysis; Fluid Therapy; Health Care Costs; Humans; Hypotension; Norepinephrine; Quality-Adjusted Life Years; Resuscitation; Retrospective Studies; Shock, Septic; Time-to-Treatment; Vasoconstrictor Agents; Vasopressins

Peri-intubation cardiac arrest and hypotension in patients with septic shock occur often in the emergency department (ED) and ultimately lead to worse clinical outcomes. In recent years, the use of push-dose, or bolus-dose, vasopressors in the ED have become common practice for transient hypotension and bridging to continuous infusion vasopressors. Push-dose epinephrine and phenylephrine are the agents used most frequently in this scenario.. A 63-year-old woman who was apneic and pulseless presented to our ED. After 4 min of cardiopulmonary resuscitation, spontaneous circulation was achieved, and the patient was intubated for airway protection. She became hypotensive with a blood pressure of 55/36 mm Hg. After receiving a 1-L bolus of lactated Ringer solution, she remained hypotensive with blood pressure of 80/51 mm Hg and a pulse of 129 beats/min. One unit of intravenous vasopressin push bolus was administered. Within 1 min, her hemodynamics improved to a blood pressure of 141/102 mm Hg and pulse of 120 beats/min. Over the next 2 h, her mean arterial pressure slowly and progressively declined from 120 to 80. No further vasoactive medications were required for approximately 120 min until norepinephrine and vasopressin was initiated for septic shock. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report discusses the use of push-dose vasopressin as an alternate vasoactive medication to improve hemodynamics in a patient with vasodilatory septic shock.

Topics: Drug Therapy, Combination; Emergency Service, Hospital; Female; Humans; Hypotension; Middle Aged; Norepinephrine; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Sensitive biomarkers are needed to rapidly identify high-risk infants after hypoxia-ischemia for neuroprotective treatment. Hypotension is a key determinant of hypoxic-ischemic neural injury, and a potent stimulus of humoral pressors including angiotensin-II and arginine vasopressin. We therefore aimed to quantify the relationship between vasopressin and angiotensin-II levels in the latent phase after hypoxia-ischemia induced by umbilical cord occlusion (UCO) with both the severity of preceding hypotension and subsequent neuronal injury.. Chronically instrumented near-term fetal sheep underwent sham-UCO or UCO for either 15 min or until mean arterial pressure was <8 mmHg. Neuronal injury was assessed after 72 h recovery.. Umbilical cord occlusion was associated with severe hypotension that recovered after UCO; two fetuses developed profound secondary hypotension within 6 h and died. Vasopressin levels but not angiotensin-II were significantly elevated 1-3 h after UCO and were closely associated with the severity of hypotension during UCO and the subsequent severity of neuronal loss in the parasagittal and lateral cortex, caudate nucleus and putamen. The Youden cut-point for vasopressin at 1 h was 180.0 pmol/L, with sensitivity 100% and specificity 92.3% for severe neuronal injury or death.. Vasopressin levels shortly after moderate-severe hypoxia-ischemia may be a useful early biomarker to guide the timely implementation of neuroprotective treatment.. It can be difficuIt to rapidly identify infants who might benefit from therapeutic hypothermia. We investigated whether increases in plasma pressor hormones early after hypoxia-ischemia were biomarkers for neonatal hypoxic-ischemic encephalopathy using near-term fetal sheep. Arginine vasopressin levels were elevated at 1-3 h after hypoxia-ischemia and were predictive of the severity of preceding hypotension and subsequent risk of severe neuronal injury or death after hypoxia-ischemia. Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Biomarkers; Blood Gas Analysis; Disease Models, Animal; Female; Fetal Hypoxia; Hydrogen-Ion Concentration; Hypotension; Hypoxia-Ischemia, Brain; Male; Nervous System Diseases; Neurons; Sheep; Umbilical Cord; Vasopressins

We describe a case of disulfiram-ethanol reaction in a patient presenting with altered mental status. The patient was found to be profoundly hypotensive, requiring multiple vasopressor agents. As the symptoms associated with disulfiram reaction are non-specific, it is important to maintain a high level of suspicion for drug reaction when caring for the undifferentiated altered and hypotensive patient.

Topics: Alcohol Deterrents; Disulfiram; Ethanol; Female; Humans; Hypotension; Middle Aged; Norepinephrine; Vasoconstrictor Agents; Vasopressins

Topics: Anesthesia; Diverticulum, Colon; Humans; Hypotension; Intestinal Perforation; Male; Middle Aged; Norepinephrine; Postoperative Complications; Receptors, Adrenergic; Sepsis; Sympathomimetics; Vasoconstrictor Agents; Vasopressins

Vasopressors such as norepinephrine are first line for support of mean arterial pressure (MAP) in the management of septic shock. Their use, however, is commonly associated with many adverse events. These detriments frequently trigger the use of alternative, noncatecholamine therapies, including vasopressin. Vasopressin deficiency is a known physiologic consequence of septic shock, and while guidelines recommend vasopressin in addition to norepinephrine, no consensus exists on the duration of deficiency or ideal time of cessation. Studies have suggested that vasopressin discontinuation prior to other vasopressors may lead to hypotension; however, data are limited. This study evaluates the optimal sequence for the discontinuation of vasopressin therapy in septic shock.. This was a 1-year retrospective study of 152 patients admitted to the medical intensive care unit (ICU) with septic shock who received concurrent norepinephrine and vasopressin for vasoactive support. Patients were excluded if death occurred on vasopressors, within 24 hours after discontinuation of vasopressors, or within 48 hours of ICU admission. The primary outcome of hemodynamic instability included incidence of hypotension after vasopressor discontinuation (2 consecutive MAPs < 60 mm Hg), fluid bolus administration, greater than 0.05 μg/kg/min increase in norepinephrine requirements, or addition of an alternative vasopressor. Secondary outcomes included time to hypotension, total vasopressor duration, arrhythmias, mortality, and length of stay.. Ninety-one patients met exclusion criteria, resulting in 61 patients for evaluation. Vasopressin was the first vasoactive therapy to be discontinued in 19 patients and last in 42 patients. Baseline characteristics and the use of potentially confounding treatments known to effect MAP were similar between groups. Discontinuation of vasopressin first was associated with a significant increase in hemodynamic instability (74% vs 16.7%,. Vasopressin discontinuation prior to cessation of norepinephrine infusion was associated with an increased risk of hemodynamic instability.

Topics: Critical Care; Female; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Outcome and Process Assessment, Health Care; Retrospective Studies; Shock, Septic; United States; Vasoconstrictor Agents; Vasopressins; Withholding Treatment

Topics: Critical Illness; Humans; Hypotension; Incidence; Vasoconstrictor Agents; Vasopressins

Patients with septic shock often require vasoactive agents for hemodynamic support; however, the optimal approach to discontinuing these agents once patients reach the recovery phase is currently unknown. The objective of this evaluation was to compare the incidence of hypotension within 24 hours based on the discontinuation order of norepinephrine (NE) and vasopressin (AVP) in patients in the recovery phase of septic shock.. Retrospective cohort study.. The medical, surgical, and neurosciences intensive care units (ICUs) at a large tertiary care academic medical center.. A total of 585 adults in the recovery phase of septic shock who received fixed-dose AVP for at least 6 hours as an adjunct to NE between September 2011 and August 2015 were included. Of these patients, 155 had AVP discontinued first, and 430 had NE discontinued first.. Hypotension was evaluated during the 24-hour period after discontinuation of the first vasoactive agent and was defined as mean arterial pressure less than 60 mm Hg with one or more of the following interventions: increased remaining vasoactive agent dose by 25%, reinstitution of the discontinued agent, or administration of at least 1 L of fluid bolus. Time to hypotension was evaluated with survival analysis, and risk of hypotension was evaluated with multivariable Cox proportional hazards regression. No significant difference between groups was noted in the incidence of hypotension within 24 hours (55% in the AVP discontinued first group vs 50% in the NE discontinued first group, p=0.28) or ICU mortality (45.2% vs 40.0%, p=0.26). After adjustment for baseline factors with multivariable Cox proportional hazards regression, having AVP discontinued first was independently associated with an increased risk of hypotension with a time-varying effect that decreased over time (HR(t) = e. In patients recovering from septic shock treated with concomitant AVP and NE, no significant difference was noted in the incidence of hypotension based on discontinuation order of these agents.

Topics: Academic Medical Centers; Aged; Cohort Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypotension; Incidence; Intensive Care Units; Male; Middle Aged; Norepinephrine; Proportional Hazards Models; Retrospective Studies; Shock, Septic; Time Factors; Vasoconstrictor Agents; Vasopressins

There is little data guiding clinicians on how to discontinue vasopressors among septic shock patients on concomitant norepinephrine (NE) and vasopressin (VP).. To determine the incidence of hypotension within 24 hours of discontinuing NE (NE DC first) versus VP (VP DC first) first in septic shock patients.. This retrospective study evaluated septic shock patients admitted to the medical intensive care unit (MICU) and surgical ICU (SICU) receiving concomitant NE and VP. Receipt of additional vasopressors, mixed shock states, expired or care withdrawn, and NE and VP discontinued simultaneously were exclusion criteria. The primary outcome was incidence of hypotension within 24 hours of first vasopressor discontinuation. Secondary outcomes included time to hypotension, hospital length of stay (LOS), ICU LOS, and ICU mortality.. A total of 80 patients were included (NE DC first [n = 35]; VP DC first [n = 45]), with a median age of 73 years and median modified Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores of 21 and 7, respectively. More patients in the NE DC first group were in the SICU (42.9% vs 20.0%; P = 0.048) with more intra-abdominal infections (40.0% vs 15.6%; P = 0.021) and fewer appropriate empirical antibiotics (62.9% vs 86.7%; P = 0.018). Hypotension within 24 hours of first agent discontinuation was higher in the VP DC first group (28.6% vs 62.2%; P = 0.004), with similar hospital LOS and ICU mortality. Multivariate analysis identified VP DC first as an independent predictor of hypotension (odds ratio = 7.2; CI = 2.3-22.7).. Among septic shock patients on concomitant NE and VP, discontinuation of VP first was associated with an increased incidence of hypotension; future prospective control trials are warranted.

Topics: Aged; Aged, 80 and over; Drug Therapy, Combination; Female; Humans; Hypotension; Incidence; Intensive Care Units; Male; Norepinephrine; Retrospective Studies; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Nesfatin-1, a peptide whose receptor is yet to be identified, has been shown to be involved in the modulation of feeding, stress, and metabolic responses. Recently, increasing evidence has supported a modulatory role of nesfatin-1 in cardiovascular activity. We have previously reported that nesfatin-1 causes an increase in blood pressure in normotensive and hypotensive rats by increasing plasma catecholamine, vasopressin, and renin levels. Recent reports suggest that nesfatin-1 may activate the central cholinergic system. However, there is no evidence showing an interaction between central nesfatin-1 and the cholinergic system. Therefore, this study aimed to determine whether the central cholinergic system may have a functional role in the nesfatin-1-induced cardiovascular effect observed in normotensive rats. Intracerebroventricular injection of nesfatin-1 caused short-term increases in mean arterial pressure and heart rate responses including bradycardic/tachycardic phases in normotensive animals. Central injection of nesfatin-1 increased the acetylcholine and choline levels in the posterior hypothalamus, as shown in microdialysis studies. Central pretreatment with the cholinergic muscarinic receptor antagonist atropine and/or nicotinic receptor antagonist mecamylamine blocked nesfatin-1-induced cardiovascular effects. In conclusion, the results show that centrally administered nesfatin-1 produces a pressor effect on blood pressure and heart rate responses including bradycardic/tachycardic phases in normotensive rats. Moreover, according to our findings, the central cholinergic system can modulate nesfatin-1-evoked cardiovascular activity.

Topics: Acetylcholine; Animals; Blood Pressure; Brain; Calcium-Binding Proteins; Catecholamines; Cholinergic Agents; DNA-Binding Proteins; Heart Rate; Hypotension; Male; Mecamylamine; Nerve Tissue Proteins; Nucleobindins; Rats, Sprague-Dawley; Vasoconstrictor Agents; Vasopressins

The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall.. To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS.. Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured.. All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L. Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Topics: Airway Obstruction; Anaphylaxis; Animals; Arterial Pressure; Bronchial Spasm; Capillary Leak Syndrome; Epinephrine; Hypotension; Neurophysins; Ovalbumin; Protein Precursors; Rats; Respiratory System; Vasopressins

Topics: Acidosis, Lactic; Acute Disease; Administration, Intravenous; Adult; Aged; Alcoholism; Anti-Bacterial Agents; Bicarbonates; Comorbidity; Confusion; Glasgow Coma Scale; Humans; Hyperlactatemia; Hypotension; Intubation, Intratracheal; Male; Norepinephrine; Respiration, Artificial; Respiratory Insufficiency; Tachycardia; Thiamine; Vasoconstrictor Agents; Vasopressins; Vitamin B Complex

Vasoplegic syndrome is an unusual cause of refractory hypotension under general anesthesia. It is commonly described in the setting of cardiac surgery, but rarely seen in noncardiac setting. We describe successful management of vasoplegic syndrome during Whipple procedure with vasopressin infusion. A high index of suspicion and prompt treatment with vasopressin can be lifesaving in patients with risk factors for vasoplegic syndrome who present with severe refractory hypotension and who respond poorly to fluid administration and routine vasopressor infusion.

Topics: Aged; Anesthesia, General; Humans; Hypotension; Male; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Care; Vasoconstrictor Agents; Vasoplegia; Vasopressins

Besides their well-established endocrine roles, vasopressin and oxytocin are also important regulators of immune function, participating in a complex neuroendocrine-immune network. In the present study, we investigated whether and how vasopressin and oxytocin could modulate lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a well-established model of experimental endotoxaemia. Male Wistar rats were previously treated i.v. with vasopressin V1 or oxytocin receptor antagonists and then received either an i.v. LPS injection to induce endotoxaemia or a saline imjection as a control. The animals were divided into two groups: in the first group, blood was collected at 2, 4 and 6 h after LPS injection; in the second group, mean arterial blood pressure (MABP) and heart rate (HR) were recorded over 6 h. Plasma vasopressin and oxytocin values were higher in LPS- compared to saline-injected animals at 2 and 4 h but returned to basal levels at 6 h. NO levels exhibited an opposite pattern, showing a progressive increase over the entire period. The previous administration of a vasopressin V1 receptor antagonist significantly reduced NO plasma concentrations at 2 and 4 h but not at 6 h. By contrast, oxytocin receptor agonist pre-treatment had no effect on the NO plasma concentration. In relation to MABP, previous treatment with vasopressin V1 receptor antagonist reversed the LPS-induced hypotension at 4 h, although this was not the case for oxytocin antagonist-treated animals. None of the antagonists affected HR. Our findings indicate that vasopressin (but not oxytocin) has effects on NO production during endotoxaemia in rats, although they do not lend support to the proposed anti-inflammatory actions of vasopressin during endotoxaemia.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Endotoxemia; Heart Rate; Hypotension; Lipopolysaccharides; Male; Nitric Oxide; Oxytocin; Pituitary Gland, Posterior; Rats; Receptors, Oxytocin; Time Factors; Vasopressins

Bone cement implantation syndrome (BCIS) is a well-known entity but is poorly understood and rarely reported. It is an important cause of perioperative morbidity and mortality in the patient undergoing cemented hip arthroplasty. BCIS is characterized by hypotension, hypoxia, cardiac arrhythmias, and increased pulmonary vascular resistance and can lead to eventual cardiac arrest if not managed properly. We hereby report a case of delayed presentation of BCIS following cemented right hip arthroplasty.

Topics: Adrenergic alpha-Agonists; Aged, 80 and over; Arthroplasty, Replacement, Hip; Bone Cements; Diagnosis, Differential; Epinephrine; Female; Humans; Hypotension; Norepinephrine; Postoperative Complications; Syndrome; Vasopressins; Ventricular Outflow Obstruction

Vasopressin may be used to treat vasodilatory hypotension in septic shock, but it is not recommended by guidelines as a first- or second-line agent. Little is known about how often the drug is used currently in septic shock.. We conducted this study to describe patterns of vasopressin use in a large cohort of U.S. adults with septic shock and to identify patient and hospital characteristics associated with vasopressin use.. This was a retrospective cohort study of adults admitted to U.S. hospitals with septic shock in the Premier healthcare database (July 2008 to June 2013). We performed multilevel mixed-effects logistic regression with hospitals as a random effect to identify factors associated with use of vasopressin alone or in combination with other vasopressors on at least 1 day of hospital admission. We calculated quotients of Akaike Information Criteria (AIC) to determine relative contributions of patient and hospital characteristics to observed variation.. Among 584,421 patients with septic shock in 532 hospitals, 100,923 (17.2%) received vasopressin. A total of 6.1% of patients receiving vasopressin received vasopressin alone, and 93.9% received vasopressin in combination with other vasopressors (up to five vasopressors in 15 different combinations). The mean monthly rate of vasopressin use increased from 14.5 to 19.6% over the study period, representing an average annual relative increase of 8% (P < 0.001). The median hospital rate of vasopressin use for septic shock was 11.7% (range, 0-69.7%). Patient demographic and clinical characteristics, including patient age (adjusted odds ratio, 0.71 for age > 85 yr compared with the reference group of age < 50 yr; 95% confidence interval, 0.69-0.74) and acute respiratory dysfunction (adjusted odds ratio, 3.25; 95% confidence interval, 3.20-3.31), were responsible for the majority of observed variation in vasopressin use (quotient of AICs, 0.56). However, hospital of admission also contributed substantially to observed variation (quotient of AICs, 0.37).. Approximately one-fifth of patients with septic shock received vasopressin, but rarely as a single vasopressor. The use of vasopressin has increased over time. The likelihood of receiving vasopressin was strongly associated with the specific hospital to which each patient was admitted.

Topics: Aged; Databases, Factual; Drug Therapy, Combination; Drug Utilization; Female; Hospitals; Humans; Hypotension; Logistic Models; Male; Middle Aged; Odds Ratio; Retrospective Studies; Shock, Septic; United States; Vasoconstrictor Agents; Vasopressins

We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most often result in fetal demise during gestation or in the first days of life and typically as a result of the Potter sequence. The premature delivery, and serendipitous early treatment with vasopressin, and then later fludrocortisone, resulted in an optimal outcome in an otherwise lethal condition.

Topics: Adult; Anuria; Base Sequence; Female; Fludrocortisone; Frameshift Mutation; Gene Deletion; High-Throughput Nucleotide Sequencing; Humans; Hypotension; Infant, Newborn; Infant, Premature; Kidney Tubules, Proximal; Molecular Sequence Data; Peptidyl-Dipeptidase A; Pregnancy; Treatment Outcome; Urogenital Abnormalities; Vasopressins

Topics: Blood Pressure; Dopamine; Female; Humans; Hypotension; Infant, Extremely Low Birth Weight; Infant, Premature; Infant, Premature, Diseases; Male; Vasopressins

Topics: Blood Pressure; Dopamine; Female; Humans; Hypotension; Infant, Extremely Low Birth Weight; Infant, Premature; Infant, Premature, Diseases; Male; Vasopressins

This study investigated the cardiovascular effects of nesfatin-1 in normotensive rats and animals subjected to hypotensive hemorrhage. Hemorrhagic hypotension was induced by withdrawal 2 mL blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP) and heart rate (HR). Intracerebroventricularly (i.c.v.) administered nesfatin-1 (100 pmol) increased MAP in both normotensive and hemorrhaged rats. Nesfatin-1 also caused bradycardia in normotensive and tachycardia in hemorrhaged rats. Centrally injected nesfatin-1 (100 pmol, i.c.v.) also increased plasma catecholamine, vasopressin and renin concentrations in control animals and potentiated the rise in all three cardiovascular mediators produced by hemorrhage. These findings indicate that centrally administered nesfatin-1 causes a pressor response in conscious normotensive and hemorrhaged rats and suggest that enhanced sympathetic activity and elevated vasopressin and renin concentrations mediate the cardiovascular effects of the peptide.

Topics: Animals; Blood Pressure; Bradycardia; Calcium-Binding Proteins; Catecholamines; Central Nervous System Agents; Disease Models, Animal; DNA-Binding Proteins; Heart Rate; Hemorrhage; Hypotension; Male; Nerve Tissue Proteins; Nucleobindins; Rats, Sprague-Dawley; Renin; Vasopressins

To determine the population pharmacokinetics of unbound hydrocortisone in critically ill neonates and infants receiving IV hydrocortisone for treatment of vasopressor-resistant hypotension and to identify patient-specific sources of pharmacokinetic variability.. Prospective observational cohort study.. Level 3 neonatal ICU.. Sixty-two critically ill neonates and infants receiving IV hydrocortisone as part of standard of care for the treatment of vasopressor-resistant hypotension: median gestational age 28 weeks (range, 23-41), median weight 1.2 kg (range, 0.5-4.4), and 29 females.. None.. Unbound baseline cortisol and postdose hydrocortisone concentrations measured from blood samples being drawn for routine laboratory tests. A one-compartment model best described the data. Allometric weight and postmenstrual age were significant covariates on unbound hydrocortisone clearance and volume of distribution. Final population estimates for clearance, volume of distribution, and baseline cortisol concentration were 20.2 L/hr, 244 L, and 1.37 ng/mL, respectively. Using the median weight and postmenstrual age of our subjects (i.e., 1.2 kg and 28 wk) in the final model, the typical unbound hydrocortisone clearance and volume of distribution were 1.0 L/hr and 4.2 L, respectively. The typical half-life for unbound hydrocortisone was 2.9 hours. A sharp and continuous increase in unbound hydrocortisone clearance was observed at 35 weeks postmenstrual age.. We report the first pharmacokinetic data for unbound hydrocortisone, the pharmacologically active moiety, in critically ill neonates and infants with vasopressor-resistant hypotension. Unbound hydrocortisone clearance increased with body weight and was faster in children with an older postmenstrual age. Unbound hydrocortisone clearance increased sharply at 35 weeks postmenstrual age and continued to mature thereafter. This study lays the groundwork for evaluating unbound hydrocortisone exposure-response relationships and drawing definitive conclusions about the dosing of IV hydrocortisone in critically ill neonates and infants with vasopressor-resistant hypotension.

Topics: Blood Pressure; Body Weight; Critical Illness; Drug Resistance; Female; Gestational Age; Half-Life; Hormones; Humans; Hydrocortisone; Hypotension; Infant; Infant, Newborn; Male; Prospective Studies; Vasopressins

To assess the ability of vasopressin to stabilize hemodynamics in infants with systemic hypotension secondary to congenital diaphragmatic hernia (CDH).. A retrospective chart review was performed to identify 13 patients with CDH treated with vasopressin for refractory hypotension to assess the effect of vasopressin on pulmonary and systemic hemodynamics and gas exchange in this setting. Data collected included demographics, respiratory support, inotropic agents, pulmonary and systemic hemodynamics, urine output, and serum and urine sodium levels during vasopressin therapy.. Vasopressin therapy increased mean arterial pressure and decreased pulmonary/systemic pressure ratio, heart rate, and fraction of inspired oxygen. In 6 of 13 patients, extracorporeal membrane oxygenation therapy was no longer indicated after treatment with vasopressin. Improvement in left ventricular function and oxygenation index after vasopressin initiation was associated with a decreased need for extracorporeal membrane oxygenation therapy. Prolonged vasopressin treatment was associated with hyponatremia, increased urine output, and increased urine sodium.. Vasopressin stabilized systemic hemodynamics without adverse effects on pulmonary hemodynamics in a subset of infants with CDH. Our results suggest a potential role for vasopressin therapy in patients with CDH with catecholamine-resistant refractory hypotension.

Topics: Blood Pressure; Female; Hemodynamics; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Hypotension; Infant; Male; Retrospective Studies; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Topics: Antipsychotic Agents; Clozapine; Drug Overdose; Emergency Service, Hospital; Female; Humans; Hypotension; Vasoconstrictor Agents; Vasopressins; Young Adult

To determine trends in pharmacotherapy for neonatal hypotension in all infants and in extremely low birth weight (ELBW, birth weight 300-1000 g) infants.. We queried the Pediatric Health Information System database for all infants ≤28 days with a diagnosis code for hypotension that were discharged between January 2001 and December 2012. Patients were excluded if they had complex congenital heart disease or cardiac surgery, sepsis or meningitis, or had extracorporeal membrane oxygenation. We determined trends in pharmacotherapy for hypotension in all infants and ELBW infants, an especially vulnerable group.. A total of 8019 hypotensive infants met study criteria. The 2 most prescribed medications were dopamine (65.3%) and dobutamine (19.9%). For 1487 hypotensive ELBW infants, the 2 most prescribed medications were dopamine (83.4%) and hydrocortisone (33%). During the study period, the use of dobutamine decreased, and hydrocortisone and vasopressin use increased for all infants and for ELBW infants.. Treatment of neonatal hypotension varies widely between institutions and individual practitioners, and pharmacotherapy for neonatal hypotension has changed over the past decade. Although dopamine and dobutamine were the most frequently used agents, their use has declined and the uses of hydrocortisone and vasopressin have increased.

Topics: Blood Pressure; Dobutamine; Dopamine; Drug Therapy; Extracorporeal Membrane Oxygenation; Female; Humans; Hydrocortisone; Hypotension; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Meningitis; Pediatrics; Retrospective Studies; Tertiary Care Centers; Time Factors; Treatment Outcome; Vasopressins

Anesthetic management for massive blood loss in liver surgery concomitant with hemodynamic instability secondary to carcinoid crisis can be challenging in the perioperative setting. Hypotension, diarrhea, facial flushing, bronchospasm, and tricuspid and pulmonic valvular diseases are the common manifestations of carcinoid syndrome. This report illustrates the importance of early recognition and treatment for signs and symptoms of carcinoid syndrome not only in the preoperative setting but also in the intraoperative phase to prevent undue cardiovascular collapse.

Topics: Adrenergic Agents; Antineoplastic Agents, Hormonal; Ephedrine; Hemodynamics; Humans; Hypotension; Liver; Liver Neoplasms; Male; Malignant Carcinoid Syndrome; Middle Aged; Monitoring, Intraoperative; Octreotide; Phenylephrine; Vasoconstrictor Agents; Vasopressins

Quetiapine is an atypical antipsychotic with known α-adrenergic antagonism. We present a case of refractory hypotension that occurred after induction of general anesthesia in a patient being treated with quetiapine. This patient was not currently taking antihypertensives and had no known cardiovascular abnormalities. We observed that the hypotension was most responsive to vasopressin. We recommend further investigation regarding the interaction of quetiapine and general anesthesia.

Topics: Adult; Anesthesia, General; Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Blood Pressure; Carbon Dioxide; Cardiac Surgical Procedures; Cyclohexanols; Dibenzothiazepines; Electronic Health Records; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Lamotrigine; Obesity, Morbid; Operating Rooms; Oxygen; Phenylephrine; Quetiapine Fumarate; Triazines; Vasoconstrictor Agents; Vasopressins; Venlafaxine Hydrochloride

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

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

We sought to perform the first characterization of vasopressin and other vasoactive mediators released during resuscitation of hypotensive trauma patients.. This institutional review board-approved study was conducted under waiver of consent. Adults with clinical evidence of acute traumatic injury and systolic blood pressure less than or equal to 90 mm Hg within 1 hour of arrival were evaluated at our Level I trauma center. Two hundred three patients were screened with 50 enrolled from February 2010 to February 2011. Demographic information was also collected. Blood samples were obtained at 0, 30, 60, 90, 120, and 240 minutes after arrival, and assays were performed for vasopressin, angiotensin II, epinephrine, and cortisol. We assessed the significance of variation in these vasoactive mediators with injury and transfusion of more than 600 mL, with adjustment for time using repeated-measures linear models in log units.. We found that vasopressin (p = 0.005) and epinephrine (p = 0.01) increased significantly with injury, while angiotensin (p = 0.60) and cortisol (p = 0.46) did not and that vasopressin (p < 0.001) and epinephrine (p = 0.004) increased significantly in patients requiring transfusion of more than 600 mL but angiotensin II (p = 0.11) and cortisol (p = 0.90) did not. Relatively low levels of vasopressin (<30 pg/mL) were observed at least once during the first 2 hours in 88% of trauma patients, and abnormally low epinephrine levels (<100 pg/mL) were observed at least once during the first 2 hours in 18% of trauma patients.. This is the first clinical trial to serially evaluate vasopressin and other vasoactive mediators following trauma during the resuscitation phase. Vasopressin, in particular, and epinephrine seem to be the key mediators produced in the human response to severe injury. A deficiency of vasopressin may contribute to intractable shock after trauma.. Prognostic/epidemiologic study, level III.

Topics: Adolescent; Adult; Aged; Angiotensin II; Blood Pressure; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Epinephrine; Female; Humans; Hydrocortisone; Hypotension; Infant; Injury Severity Score; Male; Middle Aged; Resuscitation; Time Factors; Vasopressins; Wounds and Injuries; Young Adult

The perioperative management of pheochromocytoma is challenging for anesthesiologists and persistent hypotension secondary to cathecholamine depletion after tumor resection can be refractory to treatment. A 64-year-old man underwent right adrenalectomy for treatment of massive pheochromocytoma. Doxazosin administration was started and increased gradually to 12 mg daily. He was premedicated with doxazosin on the day of the surgery. Induction was uneventful but there was a sudden increase of blood pressure with tachycardia on handling of tumor which was controlled by intravenous remifentanil, landiolol, diltiazem, and magnesium sulfate. With dissection of the tumor, the blood pressure dropped to 65/40 mmHg, which was resistant to fluid and cathecholamine treatment. After commencement of low dose vasopressin administration (two boluses of 0.08 U followed by 1.6 U x hr(-1)), blood pressure gradually recovered to normal ranges. Low dose vasopressin can be safely used to treat postadrenalectomy hypotension and also can reduce the cathecholamine dose.

Topics: Adrenal Gland Neoplasms; Adrenalectomy; Catecholamines; Drug Resistance; Humans; Hypotension; Male; Middle Aged; Pheochromocytoma; Postoperative Complications; Vasopressins

Cholecystokinin (CCK) was first described as a gastrointestinal hormone, but its receptors have been located in cardiac and vascular tissues, as well as in immune cells. Our aims were to investigate the role of CCK on lipopolysaccharide (LPS)-induced hypotension and its ability to modulate previously reported inflammatory mediators, therefore affecting cardiovascular function. To conduct these experiments, rats had their jugular vein cannulated for drug administration, and also, the femoral artery cannulated for mean arterial pressure (MAP) and heart rate records. Endotoxemia induced by LPS from Escherichia coli (1.5 mg/kg; i.v.) stimulated the release of CCK, a progressive drop in MAP, and increase in heart rate. Plasma tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), nitrate, vasopressin, and lactate levels were elevated in the endotoxemic rats. The pretreatment with proglumide (nonselective CCK antagonist; 30 mg/kg; i.p.) aggravated the hypotension and also increased plasma TNF-α and lactate levels. On the other hand, CCK (0.4 μg/kg; i.v.) administered before LPS significantly restored MAP, reduced aortic and hepatic inducible nitric oxide synthase (iNOS) production, and elevated plasma vasopressin and IL-10 concentrations; it did not affect TNF-α. Physiological CCK concentration reduced nitrite and iNOS synthesis by peritoneal macrophages, possibly through a self-regulatory IL-10-dependent mechanism. Together, these data suggest a new role for the peptide CCK in modulating MAP, possibly controlling the inflammatory response, stimulating the anti-inflammatory cytokine, IL-10, and reducing vascular and macrophage iNOS-derived nitric oxide production. Based on these findings, CCK could be used as an adjuvant therapeutic agent to improve cardiovascular function.

Topics: Animals; Aorta; Blood Pressure; Cholecystokinin; Drug Evaluation, Preclinical; Endotoxemia; Heart Rate; Hypotension; Inflammation Mediators; Interleukin-10; Lactic Acid; Lipopolysaccharides; Liver; Macrophages, Peritoneal; Male; Nitric Oxide Synthase Type II; Proglumide; Rats; Rats, Wistar; Shock, Septic; Tumor Necrosis Factor-alpha; Vasopressins

Although recent advances have led to a better understanding of the beneficial effects of vasopressin on haemodynamics in paediatric cardiac surgery, not much information is available on the adverse effects. The objective of this study was to assess the impact of intraoperative vasopressin infusion on postoperative liver, renal and haemostatic function and lactate levels in neonates undergoing cardiac surgery.. We reviewed data from 34 consecutive neonates who had undergone complex cardiac surgery. The cohort was divided into two groups according to the use of vasopressin. Seventeen patients received vasopressin [vasopressin (+) group], and 17 patients did not [vasopressin (-) group].. No differences between the groups in terms of age, weight, cardiopulmonary bypass time, Risk Adjustment for Congenital Heart Surgery-1 score or the comprehensive Aristotle score were seen. No differences in the systolic or diastolic arterial blood pressures, heart rate or inotropic score upon admission to the intensive care unit were observed between the groups. No adverse effects on the aminotransferase levels were seen. The vasopressin (+) group had higher urea and creatinine levels. All the patients except one received peritoneal dialysis on the day of surgery. Thirteen patients in the vasopressin (+) group and 7 patients in the vasopressin (-) group continued to require peritoneal dialysis on postoperative day 5 (POD 5) (P = 0.04). The platelet count had decreased to a significantly lower level in the vasopressin (+) group on POD 5 [97 x 10(3)/mm(3) (range: 40-132 x 10(3)/mm(3))]. A tendency toward a high lactate concentration was seen in the vasopressin (+) group. In comparison with the vasopressin (-) group, the number of patients whose lactate level remained above 2.0 mmol/l was higher in the vasopressin (+) group on PODs 2 and 3 (17 patients vs 8 patients, P < 0.01 and 15 patients vs 7 patients, P = 0.01, respectively).. These findings suggest that the intraoperative use of vasopressin extends the period of peritoneal dialysis, reduces platelet counts and delays the recovery of the lactate concentration. Intraoperative vasopressin infusion should not be used routinely, but only in catecholamine-refractory shock.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Biomarkers; Blood Urea Nitrogen; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Chi-Square Distribution; Creatinine; Drug Administration Schedule; Heart Defects, Congenital; Hemodynamics; Hemostasis; Humans; Hypotension; Infant; Infusions, Intravenous; International Normalized Ratio; Intraoperative Care; Kidney Diseases; Lactic Acid; Peritoneal Dialysis; Platelet Count; Platelet Transfusion; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Urea; Vasoconstrictor Agents; Vasopressins

The dynamic physiologic response of human brain death and the impact of vasopressin on successful organ transplantation is reported. A 60-year-old woman was admitted to the intensive care unit after severe traumatic brain injury resulting in brain death. Initial Cushing reflex was followed by a precipitous decrease in systemic blood pressure that was refractory to the alpha-agonist phenylephrine. After intravenous vasopressin was given, hemodynamic stability was restored and maintained until successful organ transplantation. Vasopressin, a catecholamine-sparing vasopressor and antidiuretic agent, may be an effective agent in the treatment of refractory hypotension after brain death prior to organ transplantation.

Topics: Blood Pressure; Brain Death; Female; Hemodynamics; Humans; Hypotension; Middle Aged; Organ Transplantation; Tissue and Organ Harvesting; Vasoconstrictor Agents; Vasopressins

Glucocorticoid administration to women at risk for preterm delivery is standard practice to enhance neonatal survival. However, antenatal betamethasone exposure (β-exposure) increases mean arterial pressure (MAP) in adult sheep (1.8 yr old) and results in impaired baroreflex sensitivity (BRS) for control of heart rate (HR). In the current studies we tested the hypothesis that enhanced sympathetic nervous system and hypothalamo-pituitary-adrenal (HPA) axis-mediated responses are evident at an early age in β-exposed sheep. Pregnant ewes were administered betamethasone (0.17 mg/kg twice over 24 h) or vehicle (Veh-control) on the 80th day of gestation, and offspring were delivered at full term. Female β-exposed and control offspring instrumented at age 42 ± 3 days for conscious continuous recording of MAP and HR had similar resting values at baseline. However, BRS was ~45% lower in β-exposed offspring. β-Exposed lambs allowed to suckle for 10 min had a greater elevation in MAP than Veh-control lambs (19 ± 1 vs 12 ± 2 mmHg; n = 4-5, P < 0.05). MAP was reduced by 20% from baseline via sodium nitroprusside infusion (SNP) over 10 min, which triggered a rebound increase in MAP only in β-exposed lambs. HR increased with the reduction in MAP during SNP infusion in Veh-control lambs, whereas there was no change in HR with the reduction in MAP in β-exposed lambs. Combined vasopressin-CRF injection caused greater increases in MAP in the β-exposed lambs. Cortisol and ACTH responses were higher in response to SNP hypotension in the β-exposed lambs. The data reveal enhanced sympathetic and HPA axis responses associated with impaired BRS preceding differences in resting MAP in preweanling female lambs exposed in utero to glucocorticoids. The consequences of these alterations at an early age include eventual development of higher blood pressure in this ovine model of fetal programming.

Topics: Adrenocorticotropic Hormone; Animals; Animals, Suckling; Baroreflex; Behavior, Animal; Betamethasone; Blood Pressure; Corticotropin-Releasing Hormone; Female; Heart Rate; Hydrocortisone; Hypotension; Hypothalamo-Hypophyseal System; Pregnancy; Prenatal Exposure Delayed Effects; Sheep; Sucking Behavior; Sympathetic Nervous System; Vasopressins

Topics: Adrenal Insufficiency; Adult; Amputation, Surgical; Anti-Bacterial Agents; Disseminated Intravascular Coagulation; Epoprostenol; Escherichia coli; Escherichia coli Infections; Female; Gangrene; Humans; Hydrocortisone; Hypotension; Kidney Calculi; Leg; Metatarsus; Pain; Platelet Aggregation Inhibitors; Purpura Fulminans; Shock, Septic; Vasopressins

FE 202158, ([Phe(2),Ile(3),Hgn(4),Orn(iPr)(8)]vasopressin, where Hgn is homoglutamine and iPr is isopropyl), a peptidic analog of the vasoconstrictor hormone [Arg(8)]vasopressin (AVP), was designed to be a potent, selective, and short-acting vasopressin type 1a receptor (V(1a)R) agonist. In functional reporter gene assays, FE 202158 was a potent and selective human V(1a)R agonist [EC(50) = 2.4 nM; selectivity ratio of 1:142:1107:440 versus human vasopressin type 1b receptor, vasopressin type 2 receptor (V(2)R), and oxytocin receptor, respectively] contrasting with AVP's lack of selectivity, especially versus the V(2)R (selectivity ratio of 1:18:0.2:92; human V(1a)R EC(50) = 0.24 nM). This activity and selectivity profile was confirmed in radioligand binding assays. FE 202158 was a potent vasoconstrictor in the isolated rat common iliac artery ex vivo (EC(50) = 3.6 nM versus 0.8 nM for AVP) and reduced rat ear skin blood flow after intravenous infusion in vivo (ED(50) = 4.0 versus 3.4 pmol/kg/min for AVP). The duration of its vasopressor effect by intravenous bolus in rats was as short as AVP at submaximally effective doses. FE 202158 had no V(2)R-mediated antidiuretic activity in rats by intravenous infusion at its ED(50) for reduction of ear skin blood flow, in contrast with the pronounced antidiuretic effect of AVP. Thus, FE 202158 seems suitable for treatment of conditions where V(1a)R activity is desirable but V(2)R activity is potentially deleterious, such as vasodilatory hypotension in septic shock. In addition to the desirable selectivity profile, its short-acting nature should allow dose titration with rapid onset and offset of action to optimize vasoconstriction efficacy and safety.

Topics: Animals; Antidiuretic Agents; Arginine Vasopressin; CHO Cells; Cricetinae; Cricetulus; Drug Evaluation, Preclinical; HEK293 Cells; Humans; Hypotension; Male; Molecular Targeted Therapy; Protein Binding; Rats; Rats, Wistar; Receptors, Oxytocin; Receptors, Vasopressin; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasopressins

Topics: Child, Preschool; Female; Fontan Procedure; Heart Defects, Congenital; Humans; Hypotension; Mediastinitis; Shock, Septic; Staphylococcal Infections; Surgical Wound Infection; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

There are little data regarding the discontinuation of vasoactive medications in patients recovering from septic shock. We designed this retrospective cohort study to evaluate the incidence of hypotension based on the order of removal of norepinephrine (NE) and vasopressin (AVP) in patients receiving concomitant NE and AVP infusions for the treatment of septic shock.. Consecutive patients receiving concomitant NE and AVP infusions for septic shock admitted to the intensive care units of a tertiary care academic medical center were evaluated.. Of 50 included patients, the first vasoactive medication discontinued was NE in 32 patients and AVP in 18 patients. The groups had similar Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores at shock onset and at the time of discontinuation of the first agent. Five patients who had NE discontinued first (16%) versus 10 patients who had AVP discontinued first (56%) developed hypotension within 24 hours (unadjusted relative risk, 3.6; 95% confidence interval, 1.5-4.5; P = .008). In a multivariate analysis, only discontinuation of AVP first was independently associated with hypotension (adjusted relative risk, 5.9; 95% confidence interval, 1.7-21.0; P = .006).. Discontinuation of AVP before NE may lead to a higher incidence of hypotension in patients recovering from septic shock receiving concomitant AVP and NE.

Topics: APACHE; Cohort Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypotension; Incidence; Male; Middle Aged; Multivariate Analysis; Norepinephrine; Retrospective Studies; Shock, Septic; Treatment Outcome; Vasopressins

Topics: Adrenergic alpha-Antagonists; Antipsychotic Agents; Clozapine; Epinephrine; Gastroesophageal Reflux; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Lung Neoplasms; Male; Middle Aged; Schizophrenia; Tobacco Use Disorder; Vasoconstrictor Agents; Vasopressins

Topics: Cardiotonic Agents; Female; Humans; Hypotension; Middle Aged; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Topics: Adrenal Gland Neoplasms; Catecholamines; Child; Humans; Hypotension; Intraoperative Complications; Male; Pheochromocytoma; Vasoconstrictor Agents; Vasopressins

Intravenous vasopressin at 0.01 to 0.04 units/kg/h increased median mean blood pressure from 26 mm Hg (range 18-44) to 41 mm Hg (range 17-90) by 12 hours of infusion (P=.002) and allowed weaning of catecholamines in a group of extremely low birth weight infants with refractory hypotension.

Topics: Humans; Hypotension; Infant, Extremely Low Birth Weight; Infant, Newborn; Vasopressins

Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-knockout mice with arginine vasopressin (AVP) for 2 weeks, controlling their water intake, or giving them an osmotic diuretic (sucrose) in order to determine whether central or nephrogenic mechanisms were involved. Under basal conditions, AT(1a)-knockout mice were hypotensive, had lower plasma AVP, and excreted more urine with a markedly reduced osmolality compared with wild-type mice. However, basal glomerular filtration rates were similar in both strains of mice. We isolated total lysate and membrane proteins from the inner medulla of wild-type and mutant mouse kidneys, and found that the amounts of aquaporin 2 (AQP2), adenylyl cyclases III and V/VI, and phosphorylated MAP kinases ERK 1/2 proteins were all reduced in the inner medulla of the knockout mice. Infusion of AVP raised plasma levels and blood pressure proportionally in both strains, but polyuria persisted and urine osmolality remained significantly lower in the knockout mice. Although AVP increased urine osmolality slightly in water-deprived knockout mice, this was well below the basal osmolality of wild-type mice. The diuretic response to the hyperosmotic sucrose was also impaired in the knockout mice. Neither AVP nor water rationing restored the levels of the inner medullary signaling proteins and membrane AQP2 proteins in the knockout mice. We suggest that AT(1a) receptor deletion causes polyuria and urine concentration defects by decreasing basal AVP release and impairing AVP-induced receptor signaling in the inner medulla.

Topics: Animals; Antidiuretic Agents; Aquaporin 2; Arginine Vasopressin; Hypotension; Kidney Concentrating Ability; Kidney Medulla; Mice; Mice, Knockout; Polyuria; Receptor, Angiotensin, Type 1; Receptors, Vasopressin; Vasopressins

Topics: Apnea; Brain Death; Cardiotonic Agents; Diagnostic Techniques, Neurological; Dopamine; Humans; Hypotension; Vasoconstrictor Agents; Vasopressins

Topics: Adult; Antidiuretic Agents; Cardiac Surgical Procedures; Humans; Hypotension; Male; Polyuria; Postoperative Complications; Substance Withdrawal Syndrome; Vasopressins

1. The aims of the present study were to determine the cardiovascular effects of arachidonic acid (AA) and to investigate the peripheral mechanisms mediating these effects in haemorrhage-induced hypotensive rats. 2. Acute haemorrhage was induced by withdrawing a total volume of 2.2 mL blood/100 g bodyweight over a period of 10 min. Rats were then injected with 75-300 microg, i.c.v., AA and cardiovascular changes were monitored over the next 60 min. Plasma catecholamine and vasopressin levels, as well as plasma renin activity (PRA), were measured 10 min after injection of 150 microg AA in haemorrhage-induced hypotensive awake rats. In addition, rats were pretreated with saline (1 mL/kg, i.v.), the vasopressin V(1) receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin (10 microg/kg, i.v.), the alpha(1)-adrenoceptor antagonist prazosin (500 microg/kg, i.v.), the non-specific angiotensin II receptor antagonist saralasin (250 microg/kg, i.v.) or a combination of these three antagonists 5 min before injection of AA (150 microg, i.c.v.). The effects of these antagonists on responses to AA were determined. 3. Arachidonic acid caused dose- and time-dependent increases in mean arterial pressure and heart rate and reversed hypotension in haemorrhaged rats. Haemorrhage itself produced an increase in plasma catecholamine and vasopressin levels, as well as PRA; injection of AA produced further increases in these parameters, ranging from 39-123%, under hypotensive conditions. Under hypotensive conditions, pretreatment of rats with all three receptor antagonists produced similar partial blockade of the pressor response to AA, but not the increase in heart rate. Moreover, combined administration of all three receptor antagonists prior to the i.c.v. injection of 150 microg AA completely abolished the pressor response to AA in haemorrhage-induced hypotensive rats. 4. These results indicate that centrally administered AA reverses hypotension by increasing blood pressure and heart rate in the hypotensive setting. The observed increases in plasma catecholamine and vasopressin levels, as well as PRA, mediate the pressor response to AA in haemorrhage-induced hypotensive rats.

Topics: Adrenergic alpha-1 Receptor Antagonists; Angiotensin Receptor Antagonists; Animals; Antidiuretic Hormone Receptor Antagonists; Arachidonic Acid; Blood Pressure; Cardiovascular System; Catecholamines; Consciousness; Drug Evaluation, Preclinical; Heart Rate; Hemorrhage; Hormone Antagonists; Hypotension; Injections, Intraventricular; Male; Rats; Rats, Sprague-Dawley; Signal Transduction; Vasopressins

Tachykinin neurokinin 3 receptor (NK3R) signaling has a broad role in vasopressin (VP) and oxytocin (OT) release. Hydralazine (HDZ)-induced hypotension activates NK3R expressed by magnocellular neurons, increases plasma VP and OT levels, and induces c-Fos expression in VP and OT neurons. Intraventricular pretreatment with the specific NK3R antagonist, SB-222200, eliminates the HDZ-stimulated VP and OT release. NK3R are distributed in the central pathways conveying hypotension information to the magnocellular neurons, and the NK3R antagonist could act anywhere in the pathways. Alternatively, the antagonist could act at the NK3R expressed by the magnocellular neurons. To determine whether blockade of NK3R on magnocellular neurons impairs VP and OT release to HDZ, rats were pretreated with a unilateral PVN injection of 0.15 M NaCl or SB-222200 prior to an intravenous injection of 0.15 M NaCl or HDZ. Blood samples were taken, and brains were processed for VP/c-Fos and OT/c-Fos immunohistochemistry. Intravenous injection of 0.15 M NaCl did not alter plasma hormone levels, and little c-Fos immunoreactivity was present in the PVN. Conversely, intravenous injection of HDZ increased plasma VP and OT levels and c-Fos expression in VP and OT magnocellular neurons. Intra-PVN injection of SB-222200 prior to an intravenous injection of HDZ significantly decreased c-Fos expression in both VP and OT neurons by approximately 70% and attenuated plasma VP and OT levels by 33% and 35%, respectively. Therefore, NK3R signaling in magnocellular neurons has a critical role for the release of VP and OT in response to hypotension.

Topics: Animals; Blood Pressure; Cell Nucleus; Hydralazine; Hypotension; Hypothalamus, Anterior; Immunohistochemistry; Male; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Quinolines; Rats; Rats, Inbred Strains; Receptors, Neurokinin-3; Signal Transduction; Vasopressins

Topics: Humans; Hypotension; Renal Dialysis; Vasopressins

A thirty-year-old woman was scheduled for laparoscopic myomectomy. After insertion of an epidural catheter at the L4-5 interspace, general anesthesia was induced with thiopental 250 mg followed by vecuronium 8mg intravenously to facilitate tracheal intubation. General anesthesia was maintained with sevoflurane and nitrous oxide. Just after intramyometrial injection of vasopressin, blood pressure decreased from 122/66 to 45/25 mmHg, and heart rate decreased from 52 to 45 beats x min(-1). The patient was ventilated with 100% oxygen, and we administered atropine 0.25 mg and ephedrine 16 mg intravenously. Blood pressure increased to 150/100 mmHg and heart rate increased to 135 beats x min(-1). Since electrocardiogram showed ST-segment depression and premature ventricular contraction, we administered nicorandil 3 mg followed by continuous infusion at a rate of 3 mg x hr(-1), and lidocaine 60 mg, intravenously. The ST depression and premature ventricular contraction disappeared immediately. To decrease blood pressure and heart rate, we increased inspiratory concentrations of sevoflurane and nitrous oxide and administered local anesthetics via epidural catheter, and hemodynamic parameters became gradually stable. We estimate that severe hypotension observed in this case is associated with intramyometrial injection of vasopressin. Increased blood concentration of vasopressin might cause vasoconstriction of coronary artery, increases in afterload, and/or direct myocardial depression resulting in decreased cardiac output.

Topics: Adult; Anesthesia, General; Atropine; Ephedrine; Female; Humans; Hypotension; Injections; Intraoperative Care; Intraoperative Complications; Laparoscopy; Leiomyoma; Monitoring, Intraoperative; Myometrium; Severity of Illness Index; Uterine Neoplasms; Vasopressins

A systemic inflammatory response to infection characterizes sepsis which associated to refractory hypotension, turns into severe sepsis. Our aim was to evaluate hormonal and cardiovascular alterations after experimental sepsis induced by cecal ligation and puncture (CLP). Male Wistar rats (200-250 g) were submitted to CLP or sham operation. The animals were decapitated at 0, 2, 4, 6 and 8 h after surgery for collection of blood samples for plasma osmolality, sodium and vasopressin (AVP) measurements. The mean arterial pressure (MAP) and heart rate (HR) were recorded 1 h before and to each 1 h during 5hs after surgery. The spontaneous baroreflex sensitivity and spectral analysis of HR and MAP variability were analyzed after recording. The plasma osmolality and sodium did not show any alterations compared to the sham group. MAP decreased from 3 h (85 vs.103 mm Hg, P<0.05) to 5 h in the CLP group (76 vs.106 mm Hg, P<0.05). This was accompanied by an increase in HR. The AVP plasma level was elevated at 4 h (6.0+/-1.1 vs. 1.1+/-0.2 pg/mL, P<0.05) and returned to basal levels at 8 h after CLP (2.3+/-0.5 vs. 1.9+/-0.2 pg/mL, P>0.05). A reduction in baroreflex sensitivity occurred 1 h after injury. The CLP group showed a reduction in overall variability, low-frequency power, and low/high-frequency ratio of HR and low-frequency power of MAP. The data suggest an impairment of autonomic control of the heart and vessels during polymicrobial sepsis. This reduction in autonomic nervous system activity causes the impairment of baroreflex that in turn may contribute to the reduction of vasopressin plasma levels in the late phase of severe sepsis.

Topics: Animals; Autonomic Nervous System; Autonomic Nervous System Diseases; Baroreflex; Blood Pressure; Cecum; Disease Models, Animal; Heart Rate; Hypotension; Ligation; Male; Osmolar Concentration; Peritonitis; Rats; Rats, Wistar; Sepsis; Shock, Septic; Sodium; Time Factors; Up-Regulation; Vasopressins

A 56-year-old man, treated with an angiotensin II receptor antagonist for hypertension, presented for placement of a cochlear implant during general anesthesia. Intraoperatively, there was profound hypotension that was resistant to decreasing the anesthetic depth, fluid administration, as well as bolus doses of phenylephrine, ephedrine, and epinephrine. Hypotension was eventually successfully treated with a vasopressin infusion (0.06 U/min). Vasopressin may be a useful agent in such scenarios because its effect is not dependent on either adrenergic or angiotensin receptors, both of which may be affected by angiotensin II receptor antagonists.

Topics: Humans; Hypotension; Infusions, Intravenous; Intraoperative Complications; Male; Middle Aged; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Topics: Aged; Cardiopulmonary Bypass; Humans; Hypotension; Intraoperative Complications; Male; Vasoconstrictor Agents; Vasopressins

Treatment of hypotension caused by calcium channel blocker overdose (CCB) remains a challenge. We describe the successful use of vasopressin in two patients with massive CCB overdoses in whom hypotension was unresponsive to calcium, glucagon, insulin, and conventional vasopressor therapies. While various modes of treatments have been used to treat the hypotension of CCB overdose, this is the first report to our knowledge of the successful use of vasopressin in this clinical setting.

Topics: Adult; Amlodipine; Antidotes; Blood Pressure; Calcium Channel Blockers; Diazepam; Diltiazem; Drug Overdose; Drug Therapy, Combination; Female; Humans; Hypotension; Middle Aged; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Topics: Adrenal Gland Neoplasms; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Pheochromocytoma; Vasopressins

Activation of the neurokinin 3 receptor (NK3R) by a receptor agonist, hypotension, and hyperosmolarity results in the internalization of NK3R expressed by magnocellular neurons and the release of vasopressin (VP) and oxytocin (OT) into the circulation. The contribution of NK3R activation to the release of VP and OT in response to hyperosmolarity and hypotension was evaluated by measuring the release of both hormones following pretreatment with a selective NK3R antagonist, SB-222200. Freely behaving male rats were given an intraventricular injection of either 0.15 M NaCl or 250, 500, or 1,000 pmol SB-222200, and then were administered an intravenous infusion of 2 M NaCl or 0.15 M NaCl (experiment 1), or a bolus intra injection of 0.15 M NaCl or hydralazine (HDZ), a hypotension-inducing drug (experiment 2). Blood samples were taken from indwelling arterial catheters at various time points for 1-2 h, both before and after treatments. Plasma VP and OT levels were determined by ELISA. Blockade of NK3R did not affect the baseline levels of either hormone. In contrast, pretreatment with SB-222200 significantly reduced ( approximately 60%) or abolished the release of VP and OT, respectively, to 2 M NaCl infusion. HDZ-induced VP and OT release was eliminated by pretreatment with 500 pmol SB-222200. Therefore, NK3R activation contributes significantly to the systemic release of both VP and OT in response to osmotic and hypotensive challenges.

Topics: Animals; Hydralazine; Hypotension; Hypothalamus; Infusions, Intravenous; Injections, Intraventricular; Male; Osmotic Pressure; Oxytocin; Quinolines; Rats; Receptors, Neurokinin-3; Sodium Chloride; Vasodilator Agents; Vasopressins; Water-Electrolyte Balance

A 63-year-old female with known empty sella syndrome underwent coronary artery bypass grafting surgery. She became hypotensive immediately postoperatively and this did not respond to fluid resuscitation and inotropic therapy. Surgical re-exploration was undertaken and did not reveal any surgical cause. Pulmonary artery catheterisation confirmed a profound vasodilatory component to her shock. We believe this was due to unmasking of posterior pituitary hypofunction, in particular vasopressin insufficiency, due to metabolic stress. This rapidly corrected with an exogenous vasopressin infusion.

Topics: Coronary Artery Bypass; Empty Sella Syndrome; Female; Humans; Hypotension; Middle Aged; Shock, Surgical; Vasopressins

We report the successful use of vasopressin in the management of hypotension in association with severe right ventricular (RV) failure in two patients with advanced idiopathic pulmonary arterial hypertension. Both patients were pregnant and developed systemic hypotension after delivery by Caesarean section. Placental autotransfusion and possibly oxytocin use were thought to be the major contributing factors in worsening RV function. After the use of vasopressin in both patients, cardiovascular variables improved without untoward effect on RV function, and provided rescue therapy for systemic hypotension in this setting. Vasopressin, a direct vasopressor acting via V1 receptors on the vascular endothelium, has been shown to cause pulmonary vasodilatation experimentally and in animal models of pulmonary hypertension. Its synthetic analogue, terlipressin, has been shown to reduce pulmonary vascular resistance in humans with cirrhosis. Vasopressin may therefore have differential effects on the pulmonary and systemic circulations, allowing systemic pressure to be supported without detrimental effects on the pulmonary circulation.

Topics: Adult; Anesthesia, Obstetrical; Cesarean Section; Female; Humans; Hypertension, Pulmonary; Hypotension; Postoperative Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Vasoconstrictor Agents; Vasopressins; Ventricular Dysfunction, Right

We have previously shown that centrally injected melittin, a phospholipase A(2) (PLA(2)) activator, increases blood pressure and decreases heart rate in the normotensive conscious rats. In the current study we aimed to determine the cardiovascular effects of melittin in hemorrhaged hypotensive rats and to investigate the mediation of peripheral adrenergic, vasopressinergic and renin angiotensin system in the pressor effect of centrally administrated melittin in both normotensive and hypotensive conditions. Acute hypotensive hemorrhage was performed by withdrawing a total volume of 2.2ml of blood/100g body weight over a period of 10min. Melittin was injected intracerebroventricularly (i.c.v.) at the doses of 1.5microg, 3.0microg or 6.0microg after the stabilization period of hemorrhage procedure. We also repeated previous experiments by injecting melittin (1.5microg, 3.0microg or 6.0microg; i.c.v.) to the normotensive animals. Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) in normal and hypotensive conditions and decreases in heart rate (HR) in normotensive conscious animals. In hypotensive rats, melittin injected at the dose of 6.0microg completely restored the decrease in blood pressure. Plasma adrenaline, noradrenaline, vasopressin levels and renin activity increased after melittin (3.0microg; i.c.v) administration in normal conditions. Hemorrhage, itself, produced an increase in these plasma hormone levels and melittin (3.0microg; i.c.v.) caused additional increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity in hypotensive conditions. Intravenous pretreatments of rats with prazosin (0.5mg/kg), an alpha(1) adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10microg/kg), a vasopressin V(1) receptor antagonist, or saralasin (250microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to melittin (3.0microg; i.c.v.) in both normotensive and hypotensive conditions. Besides, the combined administration of these three antagonists before melittin completely abolished the pressor responses to drug in both conditions. Results show that centrally administered melittin, a PLA(2) activator, increases blood pressure and reverses hypotension in hemorrhagic shock. The increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity mediate the pressor responses to melittin in normal an

Topics: Animals; Blood Pressure; Cardiovascular System; Epinephrine; Hemorrhage; Hypotension; Male; Melitten; Norepinephrine; Rats; Rats, Sprague-Dawley; Vasopressins

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

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

NKCC1 null mice are hypotensive, in part, from the absence of NKCC1-mediated vasoconstriction. Whether these mice have renal defects in NaCl and water handling which contribute to the hypotension is unexplored. Therefore, we asked 1) whether NKCC1 (-/-) mice have a defect in the regulation of NaCl and water balance, which might contribute to the observed hypotension and 2) whether the hypotension observed in these mice is accompanied by endocrine abnormalities and/or downregulation of renal Na+ transporter expression. Thus we performed balance studies, semiquantitative immunoblotting, and immunohistochemistry of kidney tissue from NKCC1 (+/+) and NKCC1 (-/-) mice which consumed either a high (2.8% NaCl)- or a low-NaCl (0.01% NaCl) diet for 7 days. Blood pressure was lower in NKCC1 (-/-) than NKCC1 (+/+) mice following either high or low dietary NaCl intake. Relative to wild-type mice, NKCC1 null mice had a lower plasma ANP concentration, a higher plasma renin and a higher serum K+ concentration with inappropriately low urinary K+ excretion, although serum aldosterone was either the same or only slightly increased in the mutant mice. Expression of NHE3, the alpha-subunit of the Na-K-ATPase, NCC, and NKCC2 were higher in NKCC1 null than in wild-type mice, although differences were generally greater during NaCl restriction. NKCC1 null mice had a reduced capacity to excrete free water than wild-type mice, which resulted in hypochloremia following the NaCl-deficient diet. Hypochloremia did not occur from increased aquaporin-1 (AQP1) or 2 protein expression or from redistribution of AQP2 to the apical regions of principal cells. Instead, NKCC1 null mice had a blunted increase in urinary osmolality following vasopressin administration, which should increase free water excretion and attenuate the hypochloremia. In conclusion, aldosterone release is inappropriately low in NKCC1 null mice. Moreover, the action of aldosterone and vasopressin is altered within kidneys of NKCC1 null mice, which likely contributes to their hypotension. Increased Na+ transporter expression, increased plasma renin, and reduced plasma ANP, as observed in NKCC1 null mice, should increase vascular volume and blood pressure, thus minimizing hypotension.

Topics: Aldosterone; Animals; Chlorides; Hypotension; Kidney; Mice; Mice, Transgenic; Organ Size; Renin; Sodium Channels; Sodium-Potassium-Chloride Symporters; Sodium, Dietary; Solute Carrier Family 12, Member 2; Vasopressins; Water

The present study sought to determine whether chemical destruction of peripheral catecholaminergic fibers with 6-hydroxydopamine (6OHDA) attenuates vasopressin (VP) and oxytocin (OT) secretion stimulated by hemorrhage, hypotension, and hyperosmolality. Rats received 6OHDA (100 mg/kg iv) or vehicle (1 ml/kg iv) on days 1 and 7, and experiments were performed on day 8. Serial hemorrhage (4 samples of 2 ml per 300 g body wt at 10-min intervals) increased plasma VP and OT levels in both groups; however, the increase in plasma VP and OT levels was significantly attenuated in 6OHDA-treated vs. control rats despite a significantly lower mean arterial blood pressure. Similarly, the increase in plasma VP and OT levels in response to hypotension produced by the selective arteriolar vasodilator diazoxide was significantly attenuated in 6OHDA-treated rats. In marked contrast to hemorrhage and hypotension, hyperosmolality produced by an infusion of 1 M NaCl (2 ml/h iv) stimulated increases in plasma VP and OT levels that were not different between 6OHDA-treated and control rats. In a parallel set of experiments, intravenous 6OHDA treatment reduced dopamine--hydroxylase immunoreactivity in the posterior pituitary but had no substantial effect in the hypothalamic paraventricular and supraoptic nuclei. In each experiment, the pressor response to tyramine (250 microg/kg iv) was significantly attenuated in 6OHDA-treated rats, thereby confirming that 6OHDA treatment destroyed sympathetic catecholaminergic fibers. Collectively, these findings suggest that catecholaminergic fibers located outside the blood-brain barrier contribute to VP and OT secretion during hemorrhage and arterial hypotension.

Topics: Animals; Diazoxide; Dopamine beta-Hydroxylase; Hemorrhage; Hypotension; Hypothalamus; Injections, Intravenous; Male; Oxidopamine; Oxytocin; Pituitary Gland, Posterior; Rats; Rats, Sprague-Dawley; Sympatholytics; Tyramine; Vasopressins; Water-Electrolyte Imbalance

Topics: Humans; Hypotension; Injections, Intravenous; Shock, Hemorrhagic; Vasoconstrictor Agents; Vasopressins

Topics: Adrenal Gland Neoplasms; Child; Humans; Hypotension; Male; Phenoxybenzamine; Pheochromocytoma; Vasopressins

Topics: Humans; Hypotension; Intraoperative Complications; Liver Transplantation; Male; Middle Aged; Reperfusion; Vasopressins

Due to neurotransmitter reuptake inhibition, peripheral alpha receptor blocking effects, and sodium channel blockade, severe cyclic antidepressant poisoning may lead to intractable hypotension. We report a case of severe amitriptyline toxicity, with hypotension unresponsive to direct alpha receptor agonists after pH manipulation, but improved with intravenous vasopressin. Vasopressin use in the setting of cyclic antidepressant toxicity has not been previously reported. Vasopressin may be a beneficial agent in the treatment of recalcitrant hypotension associated with poisoning or overdose. The anecdotal nature of this report must be emphasized and the use of vasopressin requires further research to define efficacy, dose, and potential side effects.

Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Drug Overdose; Humans; Hypotension; Male; Middle Aged; Vasoconstrictor Agents; Vasopressins

Labetalol is an effective antihypertensive medication frequently used to treat systemic hypertension in acute care settings, including the management of hypertension associated with a subarachnoid hemorrhage. We present a case of profound hypotension, refractory to inotropic and vasopressor therapy following an iv infusion of labetalol.. Initiation of an iv labetalol infusion resulted in good blood pressure control in a patient suffering from a Fisher grade 3 subarachnoid hemorrhage with an initial Glascow coma scale of 14/15 and mild hydrocephalus. Progressive deterioration of neurological symptoms and evidence of worsening hydrocephalus preceded the sudden development of profound hypotension (60/35 mmHg) and bradycardia with a minimum heart rate of 40 beats.min(-1). Initial resuscitative efforts included administration of intravascular fluid, hypertonic saline, atropine, adrenalin (more than 10 mg in divided doses) and noradrenalin. These measures restored the blood pressure to 80/45 with a HR of 98 beats.min(-1). Intraoperative placement of an intraventricular drain released cerebrospinal fluid under pressure with an initial intracranial pressure of 15 cm H(2)O. A combination of adrenalin, noradrenalin, dopamine and vasopressin infusions were required to restore the blood pressure to 130/65 mmHg after an additional two hours. All inotropic and vasopressor support was weaned off after the 14th hr (about two drug half-lives). The patient was awake and responsive the following day, with no obvious neurological consequences. No evidence of neurological injury, drug administration error or myocardial dysfunction was documented.. The episode of profound hypotension which occurred after initiating a labetolol infusion required maximal combined vasopressor therapy to restore the blood pressure suggesting that this patient demonstrated an extreme sensitivity to labetalol. Combination therapy with adrenergic and nonadrenergic agonists may be required for optimal treatment of profound hypotension associated with labetalol-induced vasoplegia.

Topics: Antihypertensive Agents; Bradycardia; Cardiotonic Agents; Dopamine; Epinephrine; Female; Humans; Hypotension; Intracranial Aneurysm; Labetalol; Middle Aged; Norepinephrine; Subarachnoid Hemorrhage; Time Factors; Vasoconstrictor Agents; Vasopressins

Topics: Coronary Artery Bypass; Humans; Hypotension; Milrinone; Norepinephrine; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

The septic shock is characterized by decrease in median arterial pressure; many researchers have been related a deficiency in vasopressin release during the septic shock. Lipopolysaccharide administration is used to induce septic shock model in animals. We investigated the heme-oxygenase (HO) inhibition during the endotoxemic shock-like conditions. The LPS administration induced a significant decrease in MAP (-15.4 +/- 1.2 mmHg at second hour, -25.8 +/- 8.7 mmHg at fourth hour, and -22.3 +/- 8.6 mmHg at sixth hour) with a concomitant increase in heart rate (486.3 +/- 55.0, 531.8 +/- 53.8, and 510.0 +/- 55.3 bpm, respectively), a significant decrease in diuresis (from 1.1 +/- 0.7 to 0.4 +/- 0.3/100g body weight at fourth hour), and a transitory decrease in body temperature (from 37.0 +/- 0.5 to 35.4 +/- 0.8 degrees C at second hour). An increase in plasma arginine vasopressin (AVP) concentration (from 3.2 +/- 0.9 to 19.0 +/- 5.7 pg/mL at the first hour) occurred in these animals and was present for 2 h after LPS administration, returning close to basal levels thereafter and remaining unchanged until the end of the experiment. When LPS was combined with the i.c.v. administration of HO inhibitor, we observed a sustained increase in plasma AVP concentration, attenuation in the drop of MAP, and increase in antidiuresis induced by LPS treatment. These data suggest that central HO pathway may activate a control mechanism that attenuates AVP secretion during endotoxemia and may consequently regulate the MAP and diuretic output.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Deuteroporphyrins; Diuresis; Enzyme Inhibitors; Heart Rate; Heme Oxygenase (Decyclizing); Hypotension; Lipopolysaccharides; Male; Rats; Rats, Wistar; Shock, Septic; Vasopressins

We reported anesthetic management of a patient complicated with septic shock. Catecolamines were not effective to improve severe hypotension. Therefore, vasopressin was used and this improved the severe hypotension. Vasopressin may be useful for a patient complicated with septic shock and severe hypotension.

Topics: Abdomen, Acute; Aged; Anesthesia, General; Humans; Hypotension; Male; Shock, Septic; Vasoconstrictor Agents; Vasopressins

Many recent studies suggest that vasopressin deficiency is an important cause of catecholamine-resistant hypotension with vasodilation in adults, but little is known about vasopressin deficiency in children.. To clarify the usefulness of vasopressin administration in pediatric cathecolamine-resistant hypotension with preserved ventricular contractility, urinary output and blood pressure response to vasopressin were retrospectively analyzed in 12 consecutive patients (15 instances) who were treated with vasopressin. The causes of vasodilation were central nervous system disturbance (n = 5), side-effect of drug (n = 5), and infection (n = 5). Plasma vasopressin concentration was measured six times before vasopressin administration and five times during vasopressin administration.. Patients were divided into four groups according to their response to vasopressin administration. In group 1 (n = 5), urinary output increased to > 3 mL/kg per h within 3 h after vasopressin administration. In group 2 (n = 4), urinary output increased to > 3 mL/kg per h from 3 to 5 h after vasopressin administration. In group 3 (n = 4), urinary output did not increase to > 3 mL/kg per min within 5 h after vasopressin administration, but systolic blood pressure increased to > 120% of the level at the time of vasopressin administration. All remaining patients were classified into group 4 (n = 3). Plasma vasopressin concentration were low considering the markedly hypotensive state in all six instances. Plasma vasopressin concentration during vasopressin administration were significantly increased compared with before administration (P < 0.05). No apparent side-effects were observed in this series.. Vasopressin deficiency may occur in catecholamine-resistant hypotension of pediatric patients due to various causes including central nervous system disturbance, drug induced hypotension and sepsis. Small doses of vasopressin administration seems to be very effective in such conditions by increasing blood pressure and urinary output.

Topics: Adolescent; Adult; Blood Pressure; Child; Child, Preschool; Female; Humans; Hypotension; Infant; Infant, Newborn; Male; Retrospective Studies; Urine; Vasoconstrictor Agents; Vasopressins

We report the successful use of a low-dose vasopressin (VP) infusion to recover a hypotensive crisis in patients who suffered persistent hypotension after prolonged hemorrhage during general anesthesia. VP was infused in two posthemorrhagic vasodilatory shock patients when they remained persistently hypotensive despite adequate fluid resuscitation and infusions of pharmacological doses of catecholamines. On administration of VP at 0.04 U x min(-1), systemic vascular resistance, systolic arterial pressure, and urine output were immediately increased (as compared with the values obtained just before VP), and infusion of catecholamine could be decreased. No adverse cardiac effects were observed during VP infusions in these patients. During vasodilatory shock after prolonged and severe hemorrhage, VP seems to be effective in reversing hypotension and decreasing the need for exogenous cathecholamines while preserving cardiac function and critical organ blood flow.

Topics: Anesthesia, General; Hemorrhage; Humans; Hypotension; Male; Middle Aged; Vasodilation; Vasopressins

Coronary effects of endothelin-1 and vasopressin during acute hypotension, and the role of NO and prostanoids in these effects were examined in anesthetized goats. Left circumflex coronary artery flow was measured electromagnetically, and hypotension was induced by constriction of the caudal vena cava in animals non-treated (7 goats) or treated with the inhibitor of NO synthesis N(w)-nitro-L-arginine methyl esther (L-NAME, 5 goats), the cyclooxygenase inhibitor meclofenamate (5 goats) or both drugs (5 goats). Under normotension (22 goats), mean arterial pressure averaged 93 +/- 3 mm Hg and coronary vascular conductance (CVC) 0.37 +/- 0.025 ml/min/mm Hg. Endothelin-1 (0.01-0.3 nmol) and vasopressin (0.03-1 nmol), intracoronarily injected, dose-dependently decreased CVC by up to 56% for endothelin-1 and 40% for vasopressin. During hypotension in every condition tested, mean arterial pressure decreased to approximately 60 mm Hg, and CVC only decreased during hypotension pretreated with L-NAME (23%) or L-NAME + meclofenamate (34%). Under non-treated hypotension, the decreases in CVC by endothelin-1 were augmented approximately 1.5 fold, and those by vasopressin were not modified. This increase in CVR by endothelin-1 was not affected by L-NAME and was reversed by meclofenamate or L-NAME + meclofenamate. The coronary effects of vasopressin were not modified by any of these treatments. Therefore, acute hypotension increases the coronary vasoconstriction in response to endothelin-1 but not to vasopressin. This increased response to endothelin-1 may be related to both inhibition of NO release and release of vasoconstrictor prostanoids.

Topics: Acute Disease; Anesthesia; Animals; Blood Pressure; Coronary Circulation; Cyclooxygenase Inhibitors; Disease Models, Animal; Endothelin-1; Female; Goats; Hypotension; Meclofenamic Acid; NG-Nitroarginine Methyl Ester; Nitric Oxide; Vasoconstriction; Vasopressins

A 64-year-old female patient was admitted to a general intensive care unit with sustained hypotension resulting from severe sepsis. Her admission plasma B-type natriuretic peptide was elevated (407 pg/ml), and echocardiogram displayed normal ventricular dimensions and function. The right ventricular end-diastolic diameter increased with acute fluid loading, and this coincided with a parallel increase in B-type natriuretic peptide. Subsequent fluid depletion was accompanied by a reduction in both right ventricular end-diastolic diameter and B-type natriuretic peptide. The present case indicates that acute fluid loading may alter plasma B-type natriuretic peptide levels, and highlights the importance of taking the clinical context into account when interpreting these levels.

Topics: Creatinine; Electrocardiography; Fatal Outcome; Female; Fluid Therapy; Heart Atria; Heart Ventricles; Hemofiltration; Humans; Hypotension; Intubation, Intratracheal; Middle Aged; Multiple Organ Failure; Natriuretic Peptides; Norepinephrine; Positive-Pressure Respiration; Sepsis; Shock, Septic; Ultrasonography; Vasoconstrictor Agents; Vasopressins

Recent studies demonstrate that vasopressin is useful when treating hemorrhagic and septic shock. The effect of vasopressin on systemic anaphylaxis has not been investigated except in clinical case reports. Vasopressin increases blood pressure because of vasoconstriction through the V1 receptor. Thus, we evaluated the effect of vasopressin on circulatory depression and bronchoconstriction provoked by systemic anaphylaxis and survival rates in rabbits. In the first set of experiments, 15 nonsensitized rabbits received normal saline (control) and vasopressin at 0.8 or 0.08 U/kg. In the second set, 40 sensitized rabbits received horse serum to induce anaphylaxis, and then received the same drugs as in the first set. In the first set, mean arterial pressure (MAP) in vasopressin groups increased by 18% to 24% compared with the control. Vasopressin at 0.8 U/kg decreased MAP insignificantly before the increases of MAP occurred. In the second set, vasopressin at 0.08 U/kg improved the survival rate. At 45 min after antigen challenge, 69% of the rabbits that received vasopressin at 0.08 U/kg were alive, whereas 29% of the control rabbits and 23% of the rabbits that received vasopressin at 0.8 U/kg were alive. Vasopressin increased MAP by 36% to 109% compared with the control within 5 min, however, at 2 min, vasopressin at 0.8 U/kg had no effect on MAP. Pulmonary dynamics were similar. In conclusion, vasopressin at 0.08 U/kg improved survival rates and severe hypotension provoked by systemic anaphylaxis, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.

Topics: Anaphylaxis; Animals; Blood Pressure; Electrocardiography; Female; Hemodynamics; Hypotension; Male; Rabbits; Shock, Septic; Temperature; Time Factors; Treatment Outcome; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

1. In the present study, we aimed to determine the involvement of brain thromboxane A2 (TXA2) in blood pressure decreases evoked by acute and/or graded haemorrhage in rats. 2. Sprague-Dawley rats were used throughout the study. Acute haemorrhage was achieved by withdrawing a total volume of 2.1 and 2.5 mL blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in a hypothalamic area to measure extracellular TXA2 levels. Graded haemorrhage was conducted successively by withdrawing carotid arterial blood (0.55 mL/100 g bodyweight) over a 10 s period four times (S1-S4) at 5 min intervals. Furegrelate (125, 250 and 500 microg), a TXA2 synthase inhibitor, was injected intracerebroventricularly (i.c.v.) 60 min before acute or graded haemorrhage was initiated. U-46619 (0.5, 1 and 2 microg, i.c.v.), a synthetic TXA2 analogue, was administered 5 min before acute haemorrhage (2.1 mL/100 g bodyweight). 3. Acute haemorrhage produced a severe and long-lasting decrease in blood pressure and had a tendency to increase heart rate. Both haemorrhage protocols (2.1 or 2.5 mL/100 g) generated similar approximate twofold increases in extracellular hypothalamic TXA2 levels. Intracerebroventricular furegrelate (250 microg) pretreatment completely blocked the TXA2 increases induced by acute haemorrhage. Furegrelate administration (100, 250 and 500 microg, i.c.v.) attenuated the fall in arterial pressure evoked by acute haemorrhage and caused significant increases in heart rate at all doses injected. 4. Graded haemorrhage progressively lowered arterial pressure and increased plasma vasopressin and adrenaline levels in the last period. Furegrelate-injected rats were greatly resistant to the hypotensive effect of haemorrhage for all degrees of blood removed. Plasma adrenaline and vasopressin levels were significantly elevated in furegrelate-pretreated rats compared with the saline-treated group during S2-S3 and S4, respectively. U-46619 administration caused small but statistically significant decreases in arterial pressure induced by haemorrhage. 4. The results show that acute hypotensive haemorrhage increases extracellular hypothalamic TXA2 levels. The increase in brain endogenous TXA2 levels involves a decrease in blood pressure evoked by haemorrhage because the blockade of TXA2 synthesis by furegrelate pretreatment attenuated the haemorrhagic hypotension. Increases in plasma adrenaline and vasopressin levels may mediate this effect.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Benzofurans; Blood Pressure; Disease Models, Animal; Epinephrine; Heart Rate; Hemorrhage; Hypotension; Hypothalamus; Injections, Intraventricular; Male; Rats; Rats, Sprague-Dawley; Thromboxane A2; Thromboxane-A Synthase; Time Factors; Vasoconstrictor Agents; Vasopressins

Topics: Adenosine Triphosphate; Blood Pressure; Brain Ischemia; Calcium Channels; Hemostatics; Humans; Hypotension; Muscle, Smooth, Vascular; Shock; Shock, Cardiogenic; Shock, Septic; Vasoconstrictor Agents; Vasodilation; Vasopressins

To describe the utility of vasopressin in the treatment of acute distributive shock clinically compatible with the diagnosis of aprotinin anaphylaxis.. A 57-yr-old female patient underwent repeat cardiac surgery to treat prosthetic valve endocarditis. She had received aprotinin during her first surgery 60 days ago. Despite a negative test dose of i.v. aprotinin 20,000 KIU, when aprotinin loading was initiated during the repeat surgery, the patient developed bronchospasm and hypotension secondary to acute distributive shock. Bronchospasm responded to inhaled salbutamol and ipatropium. The hypotension was refractory to high doses of phenylephrine. Two doses of i.v. vasopressin 5 U reversed the vasodilation and reestablished normal blood pressure.. Vasopressin, in association with alpha-agonists, can reverse acute refractory distributive shock following aprotinin administration.

Topics: Aprotinin; Blood Pressure; Bronchial Spasm; Cardiac Output; Cardiac Surgical Procedures; Central Venous Pressure; Endocarditis; Female; Heart Rate; Heart Valve Prosthesis; Hemostatics; Humans; Hypotension; Middle Aged; Prosthesis Failure; Reoperation; Shock; Staphylococcal Infections; Vasoconstrictor Agents; Vasopressins

Topics: Brain Injuries; Cerebrovascular Circulation; Humans; Hypotension; Oximetry; Ultrasonography, Doppler, Transcranial; Vasoconstrictor Agents; Vasopressins

In the present study, we investigated the cardiovascular effects of centrally injected U-46619, a thromboxane A(2) (TXA(2)) analog, and the central and peripheral mechanisms of these effects in hemorrhagic shock conditions. Hemorrhage was performed by withdrawing a total volume of 2.1 ml of blood/100 g body weight over a period of 10 min. Injections were made into the lateral cerebral ventricle (LCV), nucleus tractus solitarius (NTS), rostral ventrolateral medulla (RVLM) and paraventricular nucleus of hypothalamus (PVN). U-46619 (0.1, 1 and 2 microg) increased blood pressure and reversed hypotension in hemorrhagic shock. The pressor effect was dose- and time-dependent in all investigated brain areas. Heart rate changes were not significantly different in all groups. Pretreatment of rats with an injection of SQ-29548 (4 or 8 microg), a TXA(2) receptor antagonist, into the LCV, NTS, RVLM and PVN completely blocked the pressor effect of U-46619 (1 microg) injected into respective brain areas. Hemorrhage itself increased plasma adrenaline, noradrenaline, vasopressIN levels and renin activity. U-46619 (1 microg) injected into the LCV, PVN, RVLM and NTS produced additional increases in these hormone levels and in renin activity. Intravenous pretreatments of rats with prazosin (0.5 mg/kg), an alpha(1)-adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2),Arg(8)]- vasopressin (10 microg/kg), a vasopressin V(1)-receptor antagonist, or saralasin (250 microg/kg), an angiotensin II receptor antagonist, in hemorrhaged rats partially blocked the pressor response to U-46619 (1 microg) injected into the LCV, PVN, RVLM and NTS. Results show that centrally administered U-46619, a TXA(2) analog, increases blood pressure and reverses hypotension in hemorrhagic shock. Activation of central TXA(2) receptors mediates the pressor effect of the drug. Furthermore, the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity are involved in these effects.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adrenergic alpha-1 Receptor Antagonists; Angiotensin II Type 1 Receptor Blockers; Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Brain; Bridged Bicyclo Compounds, Heterocyclic; Catecholamines; Fatty Acids, Unsaturated; Heart Rate; Hemodynamics; Hemorrhage; Hydrazines; Hypotension; Injections; Injections, Intraventricular; Male; Medulla Oblongata; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Renin; Shock, Hemorrhagic; Solitary Nucleus; Thromboxane A2; Vasoconstrictor Agents; Vasopressins

Severe hypotensive haemorrhage results in a biphasic response, characterized by an initial increase in heart rate and sympathetic vasomotor activity (phase I) followed by a life-threatening hypotension, accompanied by profound sympathoinhibition and bradycardia (phase II). The phase II response is believed to be dependent on inputs from cardiopulmonary receptors, and may be triggered by the reduction in venous return and cardiac filling associated with severe haemorrhage. In this study, we tested the hypothesis that the phase II response could be reversed by venoconstriction, which is known to enhance venous return and cardiac filling, by comparing the effects of phenylephrine (which constricts veins as well as arterioles) with that of vasopressin (which constricts arterioles but not veins). In sodium pentobarbitone-anaesthetised rats, haemorrhage evoked an initial increase in heart rate (HR) and renal sympathetic activity (RSNA) followed by a large decrease in both variables to levels below the pre-haemorrhage baseline levels (phase II response). During the phase II response, an intravenous injection of phenylephrine, sufficient to restore mean arterial pressure to the pre-haemorrhage level, resulted in a gradually developing increase (over 3-4 min) in HR and RSNA back to the baseline levels. In contrast, intravenous injection of an equipressor dose of vasopressin did not result in any increase in RSNA and only a transient increase in HR. Injection of phenylephrine, but not vasopressin, also increased the pulsatile component of central venous pressure, indicative of reduced venous capacitance. The findings indicate that venoconstriction reverses the phase II sympathoinhibition and bradycardia.

Topics: Animals; Blood Pressure; Bradycardia; Heart Rate; Hemorrhage; Hypotension; Male; Phenylephrine; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System; Vasoconstriction; Vasoconstrictor Agents; Vasopressins

Vasopressin is a potent vasopressor in septic shock, but it may impair splanchnic perfusion. We compared the effects of vasopressin alone and in combination with dobutamine on systemic and splanchnic circulation and metabolism in porcine endotoxin shock.. Twelve pigs were randomized to receive either vasopressin (VASO, n = 6) or vasopressin in combination with dobutamine (DOBU, n = 6) during endotoxin shock (E. coli endotoxin infusion). Endotoxin infusion rate was increased to induce hypotension after which vasoactive drugs were started. We aimed to keep systemic mean arterial pressure (MAP) >70 mmHg by vasopressin; the goal of dobutamine infusion was to prevent decrease in cardiac output often associated with vasopressin infusion. Regional blood flows, oxygen delivery and consumption, arterial and regional lactate concentrations were measured.. Mean arterial pressure >70 mmHg was achieved in both the VASO and DOBU groups. After the primary decrease of cardiac output by vasopressin, systemic blood flow remained stable in vasopressin-treated animals. However, vasopressin as a monotherapy decreased portal venous blood flow. This was prevented by dobutamine. Vasopressin also induced splanchnic lactate release and arterial hyperlactatemia, which were not observed when dobutamine was combined with vasopressin.. Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.

Topics: Adrenergic beta-Agonists; Animals; Blood Gas Analysis; Cardiac Output; Dobutamine; Female; Fluid Therapy; Hemodynamics; Hemostatics; Hypotension; Lactic Acid; Microdialysis; Pyruvic Acid; Regional Blood Flow; Shock, Septic; Splanchnic Circulation; Swine; Vasopressins

Neurokinin 3 receptors (NK3-Rs) are expressed in the supraoptic nucleus (SON), and SON is innervated by substance P (SP)-expressing A1 neurons in the medulla. Because SP stimulates vasopressin (VP) and oxytocin release from explants of the hypothalamo-neurohypophyseal system (HNS), two hypotheses were tested: (1) SP-stimulated VP release is mediated by NK3-Rs, and (2) stimulation of the A1 pathway by hypotension activates SON NK3-Rs. Senktide, an NK3-R agonist, stimulated VP release from HNS explants, but neither a neurokinin 1 receptor antagonist [L732,138 (N-acetyl-L-tryptophan 3,5-bis(tri-fluoromethyl)benzyl ester)] nor two NK3-R antagonists (SB222200 and SB235375) prevented SP-stimulated VP release. Because the affinity of these antagonists for rat NK-Rs may limit their efficacy, NK3-R internalization was used to assess the ability of SP to activate SON NK3-Rs. Senktide, SP, or vehicle was microinjected above SON. The brain was perfused 5 min after injection and stained for NK3-R immunoreactivity. Using confocal microscopy, the number of NK3-R-immunoreactive (-IR) endosomes was counted in a 5.6(2) mu region of cytoplasm in SON neurons. Senktide, but not SP or vehicle, significantly increased the number of NK3-R-IR endosomes in the cytoplasm. When hypotension was induced with hydralazine, NK3-R internalization was observed within 5 min (p < 0.005). A decrease in cytoplasmic NK3-R immunoreactivity was observed within 15 min of hypotension. Unexpectedly, both senktide and hypotension resulted in translocation of NK3-R-IR immunoreactivity to the nucleus. Thus, although these studies do not identify SP as the NK3-R ligand, they do provide evidence for hypotension-induced release of an endogenous tachykinin in SON and evidence suggesting a role for NK3-Rs in transcription regulation.

Topics: Acetates; Animals; Catecholamines; Cell Compartmentation; Cell Nucleus; Cytoplasm; Endosomes; Hydralazine; Hypotension; Hypothalamo-Hypophyseal System; Hypothalamus, Anterior; Male; Microinjections; Microscopy, Confocal; Neurons; Oxytocin; Peptide Fragments; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Receptors, Neurokinin-1; Receptors, Neurokinin-3; Substance P; Tachykinins; Transcription, Genetic; Tryptophan; Vasopressins

We report the case of a 65-year-old man who developed norepinephrine-resistant vasoplegic syndrome after elective off-pump coronary artery bypass surgery (OPCAB). The failure of norepinephrine to improve the patient's hemodynamics prompted us to start treatment with vasopressin; within 30 minutes, the hemodynamics began to improve. After 12 hours, the patient was stable enough to be weaned from the vasopressin. He was discharged from the hospital on the 10th postoperative day. To our knowledge, ours is the 1st report of vasopressin use for vasodilatory shock after OPCAB in the English-language medical literature. Herein, we discuss the pathophysiology and management of vasoplegic syndrome--which is controversial--with special emphasis on the use of vasopressin in this situation.

Topics: Aged; Blood Pressure; Cardiac Output, High; Coronary Artery Bypass, Off-Pump; Humans; Hypotension; Male; Syndrome; Tachycardia; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

Topics: Animals; Fluid Therapy; Humans; Hypotension; Lypressin; Rats; Shock, Septic; Terlipressin; Vasoconstrictor Agents; Vasopressins

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

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

Intravenous (i.v.) administration of cytidine-5'-diphosphate choline (CDP-choline) (100, 250 and 500 mg/kg) increased blood pressure in normal rats and reversed hypotension in haemorrhagic shock. Choline (54 mg/kg; i.v.), at the dose equimolar to 250 mg/kg CDP-choline decreased blood pressure of rats in both conditions and caused the death of all hypotensive animals within 2-5 min. Equimolar dose of cytidine (124 mg/kg; i.v.) did not change cardiovascular parameters. Choline levels in plasma, lateral cerebral ventricle and hypothalamus increased after CDP-choline administration. Intracerebroventricular (i.c.v.) hemicholinium-3 pretreatment (20 microg), greatly attenuated the pressor effect of CDP-choline in both conditions. Atropine pretreatment (10 microg; i.c.v.) did not change the pressor effect of CDP-choline while mecamylamine (50 microg; i.c.v.) abolished the pressor response to drug. Besides, acetylcholine (1 micromol; i.c.v.) produced similar increases in blood pressure in normal and hypotensive conditions to that observed in CDP-choline given rats. CDP-choline (250 mg/kg; i.v.) increased plasma catecholamines and vasopressin levels but not plasma renin activity. Pretreatment of rats with either prazosin (0.5 mg/kg; i.v.) or vasopressin V(1) receptor antagonist, [beta-mercapto,beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2)-Arg(8)]vasopressin (10 microg/kg; i.v.), attenuated the pressor response to CDP-choline while simultaneous administration of these antagonists before CDP-choline injection completely blocked the pressor effect. Results show that i.v. CDP-choline increases blood pressure and reverses hypotension in haemorrhagic shock. Activation of central nicotinic cholinergic mechanisms by the increases in plasma and brain choline concentrations appears to be involved in the pressor effect of this drug. Moreover, the increases in plasma catecholamines and vasopressin levels mediate these effects.

Topics: Animals; Blood Pressure; Brain; Catecholamines; Choline; Cytidine Diphosphate Choline; Dose-Response Relationship, Drug; Hypotension; Injections, Intravenous; Male; Nootropic Agents; Rats; Rats, Wistar; Receptors, Nicotinic; Shock, Hemorrhagic; Vasopressins

Small-dose IV vasopressin infusion may be beneficial in acute brain injury patients with unstable hemodynamics who are refractory to fluid resuscitation and catecholamine vasopressors.

Topics: Brain Injuries; Catecholamines; Humans; Hypotension; Male; Middle Aged; Myocardial Ischemia; Pulmonary Edema; Resuscitation; Vasoconstrictor Agents; Vasopressins

Neiguan (PC-6) is a traditional acupoint in each forearm and overlies the trunk of the median nerve. Previous studies show that electroacupuncture (EA) at the Neiguan acupoint could improve not only myocardial ischemic dysfunction by inducing a depressor response but also recover hemorrhagic hypotension by inducing a pressor response. However, their physiological mechanisms are not yet elucidated. We investigated the pressor effect of Neiguan EA and its mechanism by focusing on left ventricular (LV) performance in a canine hemorrhagic hypotension model. We hemorrhaged 36 anesthetized and thoracotomized mongrel dogs and decreased LV end-systolic pressure (ESP) to approximately 70 mmHg (35% decrease). We obtained LV pressure-volume (P-V) data with a micromanometer catheter and a conductance catheter. One-hour Neiguan EA significantly recovered the decreased ESP, end-diastolic volume, and stroke volume by 32 +/- 13%, 27 +/- 13%, and 39 +/- 17%, respectively (P < 0.05), without changing heart rate and the slope of the end-systolic P-V relation. Neiguan EA inhibited a hemorrhage-induced increase in plasma catecholamines. However, vecuronium (neuromuscular blocking agent) administration abolished the antihypotension effect of Neiguan EA. Furthermore, Neiguan EA was much more effective than a nonacupoint thigh EA. We conclude that Neiguan EA achieved the antihypotension effect by improving LV filling of the hemorrhage-depressed LV performance despite the inhibition of the hemorrhage-increased plasma catecholamines. This pressor effect seemed to accompany an increased venous return by Neiguan EA-increased vasomotor tone and muscle pump. This study demonstrated a scientific basis for the therapeutic efficacy of acupuncture in the treatment of hemorrhagic hypotension and shock.

Topics: Animals; Blood Pressure; Catecholamines; Disease Models, Animal; Dogs; Electroacupuncture; Hypotension; Muscle, Skeletal; Nicotinic Antagonists; Shock, Hemorrhagic; Sympathetic Nervous System; Vasopressins; Vecuronium Bromide; Ventricular Function, Left

Topics: Bacillus cereus; Blood Pressure Determination; Female; Humans; Hypotension; Infant; Shock, Septic; Treatment Outcome; Vasoconstrictor Agents; Vasopressins

Medullary catecholamine and hypothalamic neurosecretory oxytocin cells are activated by hypotension, but previous studies have provided uncertain outcomes concerning their ability to respond to a purely hypovolaemic stimulus. In the present study, injections of PEG/water and pentolinium were used to elicit non-hypotensive, isosmotic hypovolaemia and isovolaemic, isosmotic hypotension, respectively, in conscious rats. Animals were sacrificed 2 h after treatment. Immunolabelling for Fos, tyrosine hydroxylase and oxytocin established that these two stimuli activate almost identical populations of catecholamine neurons in the ventrolateral and dorsomedial medulla, and very similar populations of oxytocin cells in the supraoptic and paraventricular nuclei of the hypothalamus.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Catecholamines; Hypotension; Hypovolemia; Medulla Oblongata; Neurons; Oxytocin; Paraventricular Hypothalamic Nucleus; Pentolinium Tartrate; Polyethylene Glycols; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Supraoptic Nucleus; Tyrosine 3-Monooxygenase; Vasopressins

Milrinone is a phosphodiesterase type III inhibitor with positive inotropic and vasodilatory effects. A common side effect of milrinone is hypotension from the peripheral vasodilation. Although mild elevations in serum creatinine have been described previously in the setting of milrinone-induced hypotension, acute oligoanuric renal failure requiring renal replacement therapy has not yet been described. This case report is the first to document such a result and to report the successful use of peritoneal dialysis in this setting. Previous case reports documented vasopressin as an effective alternative to catecholamines in the treatment of milrinone-induced hypotension. This report documents the use of four vasopressor agents (including vasopressin) in this patient, with only vasopressin resulting in improvement in systemic vascular resistance and blood pressure. Vasopressin may be the most effective vasopressor agent in the treatment of milrinone-induced hypotension.

Topics: Acute Kidney Injury; Adrenergic beta-Agonists; Amyloidosis; Cardiotonic Agents; Dobutamine; Drug Administration Schedule; Drug Therapy, Combination; Heart Diseases; Humans; Hypotension; Male; Middle Aged; Milrinone; Norepinephrine; Peritoneal Dialysis; Phenylephrine; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

A patient undergoing excision of phaeochromocytoma developed refractory hypotension which was complicated by significant intraoperative blood loss. Cardiovascular support with fluids, blood and noradrenaline failed to reverse the hypotension. Introduction of vasopressin successfully reversed the hypotension. The experience with this case suggests that vasopressin may be a useful adjunct in the treatment of catecholamine-resistant hypotension after phaeochromocytoma excision.

Topics: Adrenal Gland Neoplasms; Aged; Humans; Hypotension; Intraoperative Complications; Male; Norepinephrine; Pheochromocytoma; Postoperative Complications; Vasoconstrictor Agents; Vasopressins

Vasodilatory shock is a syndrome with high mortality. It is becoming evident that depletion of antidiuretic hormone (ADH) after cardiac surgery or during sepsis plays an important role in the pathogenesis of this condition. Established vasodilatory shock responds well to exogenous ADH infusion. It is possible that preventing ADH depletion at an earlier stage may abrogate the onset of vasodilatory shock, or at least reduce its severity. This paper examines the evidence supporting this concept, and the potential areas of concern in considering this particular type of hormone replacement therapy.

Topics: Animals; Cardiopulmonary Bypass; Drug Administration Schedule; Heart-Lung Machine; Humans; Hypotension; Infusions, Intravenous; Models, Animal; Pulsatile Flow; Randomized Controlled Trials as Topic; Retrospective Studies; Safety; Shock, Septic; Shock, Surgical; Vasodilation; Vasopressins

Intracerebroventricular (i.c.v.) administration of CDP-choline (0.25, 0.5, 1 and 2 micromol) induced prompt, dose- and time-dependent increase in blood pressure in normotensive rats. Equimolar dose of CDP-choline (1 micromol; i.c.v.) and choline (1 micromol; i.c.v.) caused similar increases in blood pressure while cytidine (1 micromol; i.c.v.) failed to produce any pressor effect. In haemorrhagic shock, CDP-choline (0.1, 0.25, 0.5 and 1 micromol; i.c.v.) increased blood pressure dose- and time-dependently. The complete reversal of hypotension was observed with the i.c.v. injection of CDP-choline (1 micromol) and choline (1 micromol). Cytidine (1 micromol; i.c.v.) produced small, but significant ( P<0.05) increase in blood pressure in haemorrhaged rats. Dose-related bradycardia was observed with the injection of CDP-choline in normotensive rats, but the changes in heart rate were not significantly different ( P>0.05) in hypotensive conditions. Choline levels in lateral cerebral ventricle and hypothalamus increased about nine- and fivefold, respectively, after CDP-choline (1 micromol) administration in normotensive rats. In haemorrhagic shock extracellular choline levels in hypothalamus increased sevenfold after an i.c.v. administration of CDP-choline (1 micromol). Hemicholinium-3 (20 microg; i.c.v.), a neuronal high affinity choline uptake blocker, and mecamylamine (50 microg; i.c.v.), nicotinic receptor antagonist, pretreatment abolished the pressor effect of CDP-choline in normal rats. The increase in blood pressure was also attenuated by atropine (10 microg; i.c.v.) pretreatment. Atropine blocked the bradycardic response observed after CDP-choline. In haemorrhaged rats, the pressor effect of CDP-choline was attenuated by hemicholinium-3 and mecamylamine while atropine failed to alter the pressor response to CDP-choline. I.c.v. CDP-choline increased plasma adrenaline and vasopressin levels in normal rats. Haemorrhage, itself, increased plasma catecholamines and vasopressin levels. CDP-choline (1 micromol) produced additional increases in the elevated plasma levels of these hormones. An alpha(1)-adrenoceptor blocker, prazosin (0.5 mg/kg; i.v.), or vasopressin V(1) receptor antagonist, [beta-mercapto, beta,beta-cyclopenta-methylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10 micro/kg; i.v.), pretreatments partially blocked the pressor response to CDP-choline (1 micromol; i.c.v.). Simultaneous administration of these two antagonists completely blocked

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Catecholamines; Cerebral Ventricles; Choline; Cholinergic Antagonists; Cytidine Diphosphate Choline; Dose-Response Relationship, Drug; Female; Heart Rate; Hypotension; Hypothalamus; Injections, Intraventricular; Male; Rats; Rats, Wistar; Shock, Hemorrhagic; Time Factors; Vasopressins

To investigate effects of IV administered carprofen on indices of renal function and results of serum biochemical and hematologic analyses in dogs anesthetized with acepromazine-thiopentone-isoflurane that had low blood pressure during anesthesia.. 6 healthy Beagles.. A randomized crossover study was conducted, using the following treatments: saline (0.9% NaCl solution)-saline, saline-carprofen, and carprofen-saline. Saline (0.08 ml/kg) and carprofen (4 mg/kg) were administered IV. The first treatment was administered 30 minutes before induction of anesthesia and immediately before administration of acepromazine (0.1 mg/kg, IM). Anesthesia was induced with thiopentone (25 mg/ml, IV) and maintained with inspired isoflurane (2% in oxygen). The second treatment was administered 30 minutes after onset of inhalation anesthesia. Blood gases, circulation, and ventilation were monitored. Renal function was assessed by glomerular filtration rate (GFR), using scintigraphy, serum biochemical analyses, and urinalysis. Hematologic analysis was performed. Statistical analysis was conducted, using ANOVA or Friedman ANOVA.. Values did not differ significantly among the 3 treatments. For all treatments, sedation and anesthesia caused changes in results of serum biochemical and hematologic analyses, a decrease in mean arterial blood pressure to 65 mm Hg, an increase of 115 pmol/L in angiotensin II concentration, and an increase of 100 seconds in time required to reach maximum activity counts during scintigraphy.. Carprofen administered IV before or during anesthesia did not cause detectable significant adverse effects on renal function or results of serum biochemical and hematologic analyses in healthy Beagles with low blood pressure during anesthesia.

Topics: Acepromazine; Anesthesia, Inhalation; Angiotensin II; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Chemical Analysis; Carbazoles; Cross-Over Studies; Dogs; Dopamine Antagonists; Female; Glomerular Filtration Rate; Hypnotics and Sedatives; Hypotension; Isoflurane; Kidney; Male; Radionuclide Imaging; Random Allocation; Thiopental; Urinalysis; Vasopressins

Topics: Cardiac Surgical Procedures; Follow-Up Studies; Heart Function Tests; Hemodynamics; Humans; Hypoplastic Left Heart Syndrome; Hypotension; Infant, Newborn; Male; Phenoxybenzamine; Postoperative Period; Risk Assessment; Treatment Outcome; Vasopressins

Septic shock is characterized by arteriolar vasodilation and hypotension. We have tested the hypothesis that nitric oxide arising from inducible nitric oxide synthase in the central nervous system is responsible for the deficiency in vasopressin release and consequent hypotension during experimental septic shock.. Septic shock was induced in male Wistar rats by intravenous injection of 1.5 mg/kg lipopolysaccharide. After lipopolysaccharide administration, we found a significant decrease in mean arterial pressure with a concomitant increase in heart rate, a significant decrease in diuresis, and a transitory decrease in body temperature. An increase in plasma vasopressin concentrations occurred in these animals and was present for 2 hrs after lipopolysaccharide administration, returning close to basal concentrations thereafter and remaining unchanged for the next 24 hrs. When lipopolysaccharide was combined with central administration of aminoguanidine, an inducible nitric oxide synthase inhibitor, we observed a sustained increase in plasma vasopressin concentration and in the maintenance of blood pressure at 4 and 6 hrs after lipopolysaccharide treatment compared with rats treated with lipopolysaccharide alone.. These data indicate that central nitric oxide arising from the inducible nitric oxide synthase pathway plays an important inhibitory role in vasopressin release during experimental septic shock and may be responsible for the hypotension occurring in this vasodilatory shock.

Topics: Animals; Central Nervous System; Enzyme Inhibitors; Guanidines; Hemodynamics; Hypotension; Lipopolysaccharides; Male; Nitric Oxide; Nitric Oxide Synthase; Rats; Rats, Wistar; Shock, Septic; Vasopressins

We describe the first case of Shy-Drager syndrome diagnosed on the basis of intraoperative hemodynamic changes. The initial hypertension in the supine position followed by severe hypotension after hydralazine administration, ultimately responsive to vasopressin, led to a diagnosis of Shy-Drager syndrome. We suggest that vasopressin may be the drug of choice in patients with Shy-Drager syndrome with refractory hypotension.

Topics: Adrenergic beta-Antagonists; Aged; Hemodynamics; Humans; Hypotension; Intraoperative Complications; Labetalol; Leg Ulcer; Male; Monitoring, Intraoperative; Multiple System Atrophy; Phenylephrine; Shy-Drager Syndrome; Vasoconstrictor Agents; Vasopressins

The cardiovascular effects of tetrahydroaminoacridine (tacrine; THA) were investigated in haemorrhaged rats. Intracerebroventricular (i.c.v.) injection of THA (10, 25 and 50 microg) restored blood pressure in a dose- and time-dependent manner. Atropine (10 microg, i.c.v.), a muscarinic receptor antagonist, attenuated the pressor response to THA (25 microg, i.c.v.), while mecamylamine (50 microg, i.c.v.), a nicotinic receptor antagonist, caused only a slight blockade in the pressor effect of THA. Simultaneous pretreatment with atropine and mecamylamine almost abolished the blood pressure effect of i.c.v. THA (25 microg). Haemorrhage increased plasma levels of adrenaline, noradrenaline, vasopressin and plasma renin activity. THA (25 microg, i.c.v.) administration caused additional increases in vasopressin and adrenaline levels but not of renin activity and noradrenaline levels. The reversal of hypotension by THA was greatly attenuated by administration of either prazosin, an alpha(1)-adrenoceptor antagonist (0.5 mg/kg, i.v.) or by the vasopressin V(1) receptor antagonist [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10 microg/kg, i.v.). Pretreatment of rats with both prazosin and the vasopressin antagonist simultaneously completely inhibited the pressor response. Intravenous administration of THA (1, 1.5 and 3 mg/kg) also reversed hypotension in rats. Atropine (10 microg, i.c.v.) greatly attenuated the pressor response to THA (1.5 mg/kg, i.v.), while mecamylamine (50 microg, i.c.v.) failed to change the pressor effect of THA. In anaesthetised haemorrhaged rats, THA (1.5 mg/kg, i.v.) increased blood pressure and survival time of the animals. These results show that centrally and peripherally injected THA reverses haemorrhagic hypotension and increases survival time in rats. Activation of central muscarinic and nicotinic receptors is involved in the pressor response to i.c.v. THA. The pressor effect of i.v. THA is solely mediated by central muscarinic receptors. Moreover, the increase in plasma adrenaline and vasopressin levels appears to be involved in the pressor effect of THA.

Topics: Adrenergic alpha-Antagonists; Anesthetics, Intravenous; Animals; Antidiuretic Hormone Receptor Antagonists; Atropine; Blood Pressure; Cardiovascular Agents; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Epinephrine; Female; Hypotension; Injections, Intravenous; Injections, Intraventricular; Male; Mecamylamine; Norepinephrine; Prazosin; Rats; Rats, Wistar; Renin; Shock, Hemorrhagic; Survival Analysis; Tacrine; Time Factors; Urethane; Vasopressins

Previous experiments have indicated that arterial hypotension increases plasma oxytocin (OT) levels in rats and that OT infused intravenously causes an increase in plasma renin activity (PRA). The goal of the present study was to determine whether systemic administration of an OT receptor antagonist would attenuate the increase in PRA that is normally evoked by arterial hypotension in rats. In conscious male rats, intravenous injection of hydralazine or diazoxide produced sustained hypotension and evoked a significant increase in PRA, as expected. Intravenous infusion of an OT receptor antagonist did not alter the hypotension induced by hydralazine or diazoxide, but it did markedly blunt the induced increase in PRA. The OT receptor antagonist also blunted the hypotension-evoked increase in heart rate and plasma vasopressin levels, suggesting that the antagonist may have generally disrupted afferent signaling of hypotension. Thus hypotension-evoked OT secretion may contribute to cardiovascular homeostasis by enhancing baroreceptor signals that stimulate increases in renin secretion, vasopressin secretion, and heart rate during arterial hypotension in rats.

Topics: Animals; Diazoxide; Heart Rate; Hormone Antagonists; Hydralazine; Hypotension; Kinetics; Male; Oxytocin; Rats; Rats, Sprague-Dawley; Renin; Vasodilator Agents; Vasopressins; Vasotocin

Endogenous opioids target noradrenergic locus ceruleus (LC) neurons and potently inhibit LC activity. Nonetheless, it has been difficult to demonstrate functional regulation of the LC-noradrenergic system by endogenous opioids because of the lack of effect of opiate antagonists. The present findings provide evidence that endogenous opioids regulate LC neuronal activity during the termination of a stressor. LC neuronal discharge was recorded from halothane-anesthetized rats before, during, and after hypotensive stress elicited by intravenous nitroprusside infusion. In naive rats, mean arterial blood pressure was temporally correlated with LC activity such that hypotension was associated with increased LC discharge and a return to the normotensive state was associated with a decrease in LC discharge below pre-stress values. After microinfusion of an antagonist of the stress neuropeptide corticotropin-releasing factor (CRF) into the LC, the increase in LC discharge associated with hypotension was prevented, whereas LC inhibition associated with termination of the challenge occurred at an earlier time and was of a greater magnitude. In contrast, microinfusion of naloxone into the LC completely abolished LC inhibition associated with termination of the stressor. Naloxone microinfusion did not prevent LC inhibition associated with hypertension produced by intravenous vasopressin administration, suggesting that endogenous opioids may be selectively engaged during the termination of hypotensive stress. These results provide evidence for a functional release of endogenous opioids within the LC. This action of endogenous opioids may serve to counterbalance excitatory effects of CRF on the LC-norepinephrine system, thereby limiting its activation by stress.

Topics: Animals; Blood Pressure; Corticotropin-Releasing Hormone; Hypotension; Injections, Intravenous; Locus Coeruleus; Male; Microinjections; Naloxone; Narcotic Antagonists; Neural Inhibition; Neurons; Nitroprusside; Opioid Peptides; Peptide Fragments; Rats; Rats, Sprague-Dawley; Stress, Physiological; Vasopressins

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

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

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.

Topics: Animals; Arginine Vasopressin; Arteries; Blood Pressure; Constriction, Pathologic; Denervation; Dogs; Female; Heart Conduction System; Hemodynamics; Hypotension; Male; Pressoreceptors; Reference Values; Renin; Sinus of Valsalva; Vasopressins; Vena Cava, Inferior

To determine whether vasopressin could be effective in treating the hypotension associated with phosphodiesterase III inhibition. Phosphodiesterase III inhibitors are cardiotonic agents that increase myocardial contractility and decrease vascular smooth muscle tone. The vasodilatory effect can be profound, and the resulting hypotension frequently requires the administration of catecholamine pressors.. Retrospective analysis of existing data.. The medical or surgical intensive care unit of Columbia-Presbyterian Medical Center.. Three consecutive patients receiving milrinone and requiring catecholamine pressors to maintain systolic arterial pressure of > or =90 mm Hg.. Vasopressin was administered to the three patients.. Vasopressin (0.03-0.07 units/min) increased systolic arterial pressure from 90+/-4.7 to 130+/-2.3 mm Hg while reducing the administration of catecholamine pressors.. Vasopressin at very low doses appears to be an effective vasopressor for milrinone-induced hypotension.

Topics: Aged; Aged, 80 and over; Cardiotonic Agents; Coronary Artery Bypass; Fatal Outcome; Female; Heart Valve Prosthesis Implantation; Humans; Hypotension; Male; Milrinone; Mitral Valve; Norepinephrine; Phosphodiesterase Inhibitors; Postoperative Period; Retrospective Studies; Vasoconstrictor Agents; Vasopressins

The studies were designed to test for effects of acute increases in estradiol and progesterone, similar in magnitude and duration to those in the ovine estrous cycle, on adrenocorticotropic hormone (ACTH) and plasma vasopressin (AVP) under resting conditions and in response to hypotension. Ewes (7 per group) were studied as intact, ovariectomized, ovariectomized and treated with progesterone for 7-8 days, or subsequently treated with estradiol. During progesterone treatment plasma sodium and AVP were increased significantly. However, neither plasma volume nor blood pressure was altered. Plasma AVP responses to hypotension were not altered by either progesterone or estradiol treatment. The peak plasma ACTH response to hypotension was not altered by steroid treatment; however, the duration of the response was greater in progesterone-treated ewes than in intact ewes. The results indicate that changes in gonadal steroids similar to those in the ovine estrous cycle cause a small increase in plasma sodium that stimulates AVP, but do not alter regulation of blood pressure or volume or AVP or ACTH responses to hypotension.

Topics: Adrenocorticotropic Hormone; Animals; Blood Pressure; Estradiol; Estrus; Female; Hydrocortisone; Hypotension; Nitroprusside; Ovariectomy; Plasma Volume; Progesterone; Sheep; Sodium; Vasopressins

The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Blood Pressure; Cyclic Nucleotide Phosphodiesterases, Type 3; Heart Failure; Humans; Hypotension; Injections, Intravenous; Milrinone; Myocardial Contraction; Phosphodiesterase Inhibitors; Pulmonary Wedge Pressure; Retrospective Studies; Treatment Outcome; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

Topics: Aged; Angiography; Aortic Valve Stenosis; Cardiopulmonary Bypass; Echocardiography; Female; Hemodynamics; Humans; Hypotension; Vasoconstrictor Agents; Vasopressins

Plasma vasoactive hormone concentrations [epinephrine (p(Epi)), norepinephrine (p(NE)), ANG II (p(ANG II)), vasopressin (p(VP)), endothelin-1 (p(ET-1))] and plasma renin activity (p(RA)) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol. kg(-1). day(-1) Na(+)) were exposed to 30 min of LBNP from -15 to -50 mmHg. LBNP was uneventful for seven men [25 +/- 2 yr, high-tolerance (HiTol) group], but eight men (26 +/- 3 yr) reached presyncope after 11 +/- 1 min [P < 0.001, low-tolerance (LoTol) group]. Mean arterial pressure (MAP) did not change measurably, but central venous pressure and left atrial diameter decreased similarly in both groups (5-6 mmHg, by approximately 30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were similar between groups, however, p(RA) differed between them (LoTol 0.6 +/- 0.1, HiTol 1.2 +/- 0.1 ng ANG I. ml(-1). h(-1), P < 0.05). LBNP increased (P < 0. 05) p(RA) and p(ANG II), respectively, more in the HiTol group (9.9 +/- 2.2 ng ANG I. ml(-1). h(-1) and 58 +/- 12 pg/ml) than in LoTol subjects (4.3 +/- 0.9 ng ANG I. ml(-1). h(-1) and 28 +/- 6 pg/ml). In contrast, the increase in p(VP) was higher (P < 0.05) in the LoTol than in the HiTol group. The increases (P < 0.05) for p(NE) were nonsignificant between groups, and p(ET-1) remained unchanged. Thus there may be a causal relationship between attenuated activation of p(RA) and p(ANG II) and presyncope, with p(VP) being a possible cofactor. Measurement of resting p(RA) may be of predictive value for those with lower hypotensive tolerance.

Topics: Adaptation, Physiological; Adult; Blood Pressure; Central Venous Pressure; Epinephrine; Humans; Hypotension; Lower Body Negative Pressure; Male; Norepinephrine; Plasma Volume; Renin-Angiotensin System; Vasopressins

Topics: Cardiopulmonary Bypass; Humans; Hypotension; Postoperative Complications; Vasopressins

Hypovolemic shock of marked severity and duration may progress to cardiovascular collapse unresponsive to volume replacement and drug intervention. On the basis of clinical observations, we investigated the action of vasopressin in an animal model of this condition.. In 7 dogs, prolonged hemorrhagic shock (mean arterial pressure [MAP] of approximately 40 mm Hg) was induced by exsanguination into a reservoir. After approximately 30 minutes, progressive reinfusion was needed to maintain MAP at approximately 40 mm Hg, and by approximately 1 hour, despite complete restoration of blood volume, the administration of norepinephrine approximately 3 micrograms . kg(-1). min(-1) was required to maintain this pressure. At this moment, administration of vasopressin 1 to 4 mU. kg(-1). min(-1) increased MAP from 39+/-6 to 128+/-9 mm Hg (P<0.001), primarily because of peripheral vasoconstriction. In 3 dogs subjected to similar prolonged hemorrhagic shock, angiotensin II 180 ng. kg(-1). min(-1) had only a marginal effect on MAP (45+/-12 to 49+/-15 mm Hg). Plasma vasopressin was markedly elevated during acute hemorrhage but fell from 319+/-66 to 29+/-9 pg/mL before administration of vasopressin (P<0.01).. Vasopressin is a uniquely effective pressor in the irreversible phase of hemorrhagic shock unresponsive to volume replacement and catecholamine vasopressors. Vasopressin deficiency may contribute to the pathogenesis of this condition.

Topics: Adult; Animals; Blood Pressure; Dogs; Female; Humans; Hypotension; Middle Aged; Shock, Hemorrhagic; Vasoconstrictor Agents; Vasopressins

Hormonal systems such as vasopressin (AVP) and the renin-angiotensin-aldosterone system (RAS) have been reported to become activated during anesthesia and surgery. The purpose of this study was to examine the relative importance of AVP and angiotensin II (AII) in blood pressure control during isoflurane anesthesia in rats.. Rats were given an AVP V1-receptor antagonist (AVP-a, 10 microg kg(-1)), the AII receptor antagonist saralasin (SAR, 20 microg kg(-1) min(-1)) and hexamethonium (HEX, 10 mg kg(-1)) intravenously in random order, awake or anesthetized with isoflurane.. AVP-a had no effect on mean arterial pressure (MAP) in awake or anesthetized animals, but reduced MAP by 20.0+/-2.2% in the anesthetized rats which previously had been treated with SAR and/or HEX. SAR infusion had no effect on MAP when administered to conscious rats, but decreased MAP by 12.0+/-4.4% during anesthesia. Ganglionic blockade with HEX consistently lowered MAP in the conscious and anesthetized animals.. It is concluded that AVP contributes to the maintenance of blood pressure when the autonomic nervous system (ANS) and/or RAS are blocked during isoflurane anesthesia. SAR infusion leads to hypotension during anesthesia, but not in conscious rats. These findings indicate that AII is of importance for blood pressure maintenance during isoflurane anesthesia in rats, and that apparent pressor effects of AVP come into play when RAS and/or ANS are blocked.

Topics: Anesthesia, Inhalation; Anesthetics, Inhalation; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Arginine Vasopressin; Autonomic Nervous System; Blood Pressure; Consciousness; Ganglionic Blockers; Hexamethonium; Hormone Antagonists; Hypotension; Infusions, Intravenous; Isoflurane; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Saralasin; Vasoconstrictor Agents; Vasopressins

We report the solid phase synthesis and vasodepressor potencies of the novel hypotensive peptide [1(-beta-mercapto-beta,beta-pentamethylene propionic acid)-2-O-ethyl-D-tyrosine, 3-arginine, 4-valine] arginine vasopressin, d(CH2)5[D-Tyr(Et)2, Arg3, Val4]AVP (A), its related Lys3 (B), Tyr-NH(9)2 (C), [Lys3, Tyr-NH(9)2 (D) analogs and in a preliminary structure-activity study of positions 2-4 and 7-9, 24 analogs (1-24) of A-C. Peptides 1-6, 9-14 have the following single substituents at positions 2, 3, 4, 8 and 9 in (A): 1, D-Tyr(Me)2; 2, L-Tyr(Et)2; 3, Orn3; 4, N-Me-Arg3; 5, Glu3; 6, Arg4; 9, D-Arg8; 10, Eda9; 11, Arg-NH(9)2; 12, Ala-NH(9)2; 13, desGly9; 14, desGly-NH(9)2. Peptides 15 and 16 are analogs of B which possess the following single modifications: 15, Arg-NH(9)2; 16, desGly9. Peptides 7 and 8 are analogs of (C) with the following single modification: 7, Gln4; 8, Lys8. Peptides 17-24 are analogs of A possessing the following multiple modifications: 17, [Sar7, Eda9]; 18, [Arg7, Eda9]; 19, [Arg7, Eda9<--Tyr10]; 20, [Arg4, Arg-NH(9)2]; 21, [Ile4, desGly9]; 22, [Arg4, desGly9]l; 23, [Arg7, desGly9]; 24, [Arg7, Lys8, desGly9]. All 24 new peptides were evaluated for agonistic and antagonistic activities in in vivo antidiuretic (V2-receptor), vasopressor (V1a-receptor) and in in vitro (no Mg2+) oxytocic (OT-receptor) assays and like the parent peptides (A-D) (Chan et al. Br. J. Pharmacol. 1998; 125: 803-811) were found to exhibit no or negligible activities in these assays. Vasodepressor potencies were determined in anesthetized male rats with baseline mean arterial blood pressure maintained at 110-120 mmHg. The effective dose (ED), in microg 100 g(-1) i.v., required to produce a vasodepressor response of 5 cm2, area under the vasodepressor response curve (AUC) during the 5-min period following the injection of the test peptide, was determined. Therefore, the EDs measure the relative vasodepressor potencies of the hypotensive peptides. The following ED values were obtained for A-D and for peptides 1-24: A, 4.66; B, 5.75; C, 10.56; D, 11.60; 1, approximately 20; 2, approximately 30; 3, 6.78; 4, non-detectable (ND); 5, ND; 6, approximately 32; 7, ND; 8, 8.67; 9, ND; 10, 2.43; 11, 3.54; 12, 10.57; 13, 4.81; 14, ND; 15, 4.47; 16, 9.78; 17, 5.72; 18, 1.10; 19, 1.05; 20, 10.41; 21, 9.13; 22, approximately 33; 23, 3.01; 24, 1.71. A is clearly the most potent of the four original hypotensive peptides A-D. These data provide insights to which modification of A enh

Topics: Arginine Vasopressin; Hypotension; Molecular Structure; Receptors, Vasopressin; Structure-Activity Relationship; Vasodilator Agents; Vasopressins

Intracerebroventricular (i.c.v.) choline (50-150 microg) increased blood pressure and decreased heart rate in spinal cord transected, hypotensive rats. Choline administered intraperitoneally (60 mg/kg), also, increased blood pressure, but to a lesser extent. The pressor response to i.c.v. choline was associated with an increase in plasma vasopressin. Mecamylamine pretreatment (50 microg; i.c.v.) blocked the pressor, bradycardic and vasopressin responses to choline (150 microg). Atropine pretreatment (10 microg; i.c.v.) abolished the bradycardia but failed to alter pressor and vasopressin responses. Hemicholinium-3 [HC-3 (20 microg; i.c.v.)] pretreatment attenuated both bradycardia and pressor responses to choline. The vasopressin V1 receptor antagonist, (beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2, Arg8)-vasopressin (10 microg/kg) administered intravenously 5 min after choline abolished the pressor response and attenuated the bradycardia-induced by choline. These data show that choline restores hypotension effectively by activating central nicotinic receptors via presynaptic mechanisms, in spinal shock. Choline-induced bradycardia is mediated by central nicotinic and muscarinic receptors. Increase in plasma vasopressin is involved in cardiovascular effects of choline.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Atropine; Blood Pressure; Cerebral Ventricles; Choline; Dose-Response Relationship, Drug; Heart Rate; Hemicholinium 3; Hormone Antagonists; Hypotension; Injections, Intraventricular; Male; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Injuries; Time Factors; Vasopressins

Topics: Aortic Valve Stenosis; Blood Pressure; Cardiac Output; Cardiopulmonary Bypass; Cardiotonic Agents; Central Venous Pressure; Female; Heart Rate; Heart Valve Prosthesis Implantation; Humans; Hypotension; Middle Aged; Mitral Valve; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

Topics: Aged; Aged, 80 and over; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiopulmonary Bypass; Drug Therapy, Combination; Follow-Up Studies; Heart Failure; Heart Transplantation; Humans; Hypotension; Male; Middle Aged; Vasodilation; Vasodilator Agents; Vasopressins

Systemic hypotension may result in postoperative renal failure in jaundiced patients. Attenuated responsiveness to catecholamines and hypovolaemia has been reported in jaundiced animals and may be a mechanism contributing to the increased susceptibility of jaundiced patients to haemorrhagic shock. This suggests that an alternative to vasoactive amines to control perioperative hypotension could be desirable.. This study evaluated the pressor response to vasopressin in normovolaemic 3-day bile duct-ligated rats and in 3-day bile duct-ligated rats after an acute controlled haemorrhage. It also evaluated the response after volume loading with 0.9 per cent saline, 7.5 per cent saline, colloid and mannitol before controlled haemorrhage. In addition, blood volume was measured using radiolabelled albumin. All the data obtained from bile duct-ligated rats were compared with data from sham-operated animals.. Attenuated pressor responses to vasopressin were not observed in either normotensive bile duct-ligated rats or in the bile duct-ligated rats subjected to controlled haemorrhage. Volume loading with the four fluids over the dosing range 2.5-7.5 microliters per g body-weight in bile duct-ligated rats reversed the susceptibility to haemorrhagic hypotension.. Although no reduction in blood volume was demonstrated, bile duct-ligated rats may have a reduced effective blood volume manifesting itself as a latent hypovolaemia and/or tendency to hypotension. Preoperative fluid loading could be beneficial because it corrects hypovolaemia and improves cardiovascular function, as well as improving the cardiovascular response to haemorrhage.

Topics: Animals; Bile Ducts; Blood Pressure; Blood Volume; Female; Hemorrhage; Hypotension; Ligation; Random Allocation; Rats; Rats, Sprague-Dawley; Therapeutic Irrigation; Vasopressins

1. The effect of centrally administered choline on blood pressure was investigated in rats made hypotensive by chemical sympathectomy. Chemical sympathectomy was produced by intravenous (i.v.) injection of 50 mg kg-1 of 6-hydroxydopamine (6-OHDA). Intracerebroventricular (i.c.v.) administration of choline (50-150 micrograms) 2 h after 6-OHDA treatment increased blood pressure and reversed the hypotension in a dose-dependent manner without affecting the heart rate. The pressor response was associated with an increase in plasma vasopressin levels. 2. Pretreatment of rats with the nicotinic receptor antagonist, mecamylamine (50 micrograms, i.c.v.), but not the muscarinic receptor antagonist atropine (10 micrograms, i.c.v.), blocked both the pressor and vasopressin responses to choline (150 micrograms). Pretreatment of rats with hemicholinium-3 (HC-3), a high affinity choline uptake inhibitor, greatly attenuated the pressor response to i.c.v. choline (150 micrograms). 3. The vasopressin V1 receptor antagonist, beta-mercapto-beta,beta-cyclopentamethylenepropionyl-O-Me-Try,Arg) - vasopressin (10 micrograms kg-1; i.v.) given 5 min after i.c.v. choline, decreased the blood pressure but failed to return it to the pre-choline levels. Prazosine (0.5 mg kg-1; i.p.), an antagonist of alpha-adrenoceptors, also decreased blood pressure. Administration of both antagonists together eliminated the pressor response to choline, and the blood pressure was reduced further to below the pre-choline levels. 4. It is concluded that i.c.v. choline can increase blood pressure in rats made hypotensive by acute chemical sympathectomy through the activation of central nicotinic receptors by presynaptic mechanisms. An elevation in plasma levels of both vasopressin and catecholamines (possibly released from the adrenal medulla) is involved in the pressor response to choline.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Pressure; Choline; Cholinergic Antagonists; Dose-Response Relationship, Drug; Heart Rate; Hypotension; Injections, Intravenous; Injections, Intraventricular; Male; Oxidopamine; Prazosin; Rats; Rats, Wistar; Receptors, Cholinergic; Sympathectomy, Chemical; Vasopressins

Topics: Animals; Bile Ducts; Hypotension; Ligation; Rats; Vascular Resistance; Vasoconstrictor Agents; Vasopressins

Hemorrhage and nonhypotensive hypovolemia are known to increase plasma levels of oxytocin (OT) and vasopressin (VP) in rats. The present experiments demonstrated that secretion of OT and VP also are stimulated by acute drug-induced hypotension. Injection of hydralazine abruptly decreased arterial blood pressure in conscious rats and induced Fos expression, a marker of neuronal activation, within OT and VP neurons in the hypothalamus. Hydralazine also elicited substantial increases in plasma levels of both OT and VP. Injection of chlorisondamine similarly elicited acute hypotension and increased plasma levels of OT and VP. Furthermore, when the hypotensive effect of chlorisondamine was blunted by coinfusion of phenylephrine, the induced increases in OT and VP were markedly attenuated. Across all treatments, arterial blood pressure was inversely related to plasma levels of OT and VP. Plasma osmolality was not increased by hydralazine, nor was there evidence of gastric malaise, two known stimuli for OT secretion in rats. These results suggest that arterial hypotension increases neurohypophysial release of OT and VP in conscious rats.

Topics: Animals; Antihypertensive Agents; Avoidance Learning; Blood Pressure; Chlorisondamine; Conditioning, Psychological; Hydralazine; Hypotension; Hypothalamus; Male; Neurons; Oxytocin; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Saccharin; Taste; Vasopressins

The cardiovascular effects of intracerebroventricular (i.c.v.) administration of choline were studied in endotoxin-treated rats. Intravenous (i.v.) endotoxin (20 mg/kg) caused a moderate hypotension and tachycardia within 10 min of treatment. Choline (50, 100, and 150 microg; i.c.v.) increased blood pressure and decreased heart rate in this condition in a dose-dependent manner. Mecamylamine (50 microg; i.c.v.) pretreatment prevented the pressor and bradycardic responses to choline, whereas atropine (10 microg; i.c.v.) failed to alter both responses. Atropine pretreatment, alone, inhibited endotoxin-induced hypotension. The pressor responses to choline in endotoxin-treated rats were attenuated by pretreatment with hemicholinium-3 (20 microg; i.c.v.), a high-affinity neuronal choline-uptake inhibitor. Plasma vasopressin levels of endotoxin-treated rats were severalfold higher than those of control animals, and choline (50-150 microg; i.c.v.) produced further increases in plasma vasopressin in this condition. Mecamylamine abolished vasopressin response to endotoxin as well as to choline. The vasopressin receptor antagonist, (beta-mercapto-beta,beta-cyclopentamethylene-propionyl(1)-O-Me-Tyr2,Arg8 )-vasopressin (10 microg/kg; i.v.) administered 5 min after choline decreased blood pressure from the increased level to the precholine levels but did not alter bradycardia. These results indicate that, in rats treated with endotoxin, choline increases blood pressure and decreases heart rate by a presynaptic mechanism leading to the activation of central nicotinic cholinergic pathways. An increase in plasma vasopressin levels seems to be involved in the pressor, but not in the bradycardic response, to choline.

Topics: Animals; Blood Pressure; Choline; Cholinergic Agents; Dose-Response Relationship, Drug; Endotoxins; Heart Rate; Hormone Antagonists; Hypotension; Injections, Intravenous; Injections, Intraventricular; Male; Muscarinic Antagonists; Nicotinic Antagonists; Rats; Rats, Wistar; Shock, Septic; Tachycardia; Vasopressins

Vasopressin is now commonly used to control bleeding during surgery of the cervix. In larger intravenous doses, vasopressin can cause coronary artery vasoconstriction and increase systemic vascular resistance. Nicotine has a similar effect on the coronary circulation. The effects of combining both these drugs has not been studied. We describe a 22-year-old woman who developed severe hypotension and bradycardia after receiving a small dose of paracervical vasopressin. She was using a transdermal nicotine patch at the time of her surgery. We suspect her cardiac problems, and recently reported cardiac events in other women receiving small doses of paracervical vasopressin, could be caused by a synergism of the vasoconstrictive properties of nicotine and vasopressin. Caution is urged when vasopressin is to be administered to patients who smoke or use nicotine transdermal patches.

Topics: Administration, Cutaneous; Adult; Bradycardia; Cervix Uteri; Conization; Drug Synergism; Female; Heart Rate; Humans; Hypotension; Nicotine; Smoking Cessation; Tobacco Use Disorder; Uterine Cervical Dysplasia; Vasopressins; Vulvar Diseases

1. The release of vasopressin from the neurohypophysial terminals of hypothalamic magnocellular neurosecretory neurons is subject to regulation by peripheral baroreceptors, cardiopulmonary volume receptors and circulating angiotensin II. Information from these sources is transmitted through different pathways to achieve different influences on the excitability of the vasopressin-secreting cells. 2. A brief increase in arterial pressure, sufficient to activate baroreceptors, is associated with a transient and selective GABAergic inhibition of these neurosecretory neurons, achieved through a multisynaptic pathway that involves ascending catecholaminergic fibres and neurons in the diagonal band of Broca. A decrease in arterial pressure activates peripheral low volume receptors and initiating neural inputs that result in an increase in the excitability of vasopressin-secreting neurons, achieved via pathways that include direct projections from caudal ventrolateral medulla A1 neurons. 3. Hypotension also releases renal renin and leads to the formation of angiotensin II; binding of this hormone to AT1 receptors on subfornical organ neurons promotes activation of a central angiotensinergic input that evokes a predominantly excitatory effect on vasopressin neurons.

Topics: Angiotensin II; Blood Pressure; Cardiovascular Physiological Phenomena; Hypotension; Hypothalamus; Neurosecretory Systems; Pressoreceptors; Shock; Subfornical Organ; Vasopressins

The effect of intracerebrovenricularly (i.c.v.) injected choline on blood pressure was investigated in rats made hypotensive by blocking peripheral alpha-adrenoceptors or autonomic ganglionic transmission. Choline (50-150 micrograms; i.c.v.) increased blood pressure in a dose-dependent manner and 150 micrograms of choline restored blood pressure to the resting level. The pressor response to choline was associated with an increase in plasma vasopressin levels. Pretreatment with mecamylamine (50 micrograms; i.c.v.), but not atropine (10 micrograms; i.c.v.), blocked both the pressor and vasopressin responses to i.c.v. choline. The vasopressin receptor antagonist, [beta-mercapto-beta,beta-cyclopenta-methylene-propionyl1,O-Me-T ry2,Arg8] vasopressin (10 micrograms/kg; i.v.), given 5 min after i.c.v. choline (150 micrograms), abolished the pressor effect of choline and blood pressure returned to the pre-choline levels. It is concluded that the precursor of acetylcholine, choline, can increase blood pressure and reverse hypotension in alpha-adrenoceptor or ganglionic transmission blocked rats, by increasing plasma vasopressin.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Analysis of Variance; Animals; Blood Pressure; Choline; Dose-Response Relationship, Drug; Ganglionic Blockers; Heart Rate; Hexamethonium; Hypotension; Male; Mecamylamine; Nicotinic Antagonists; Nootropic Agents; Phentolamine; Propranolol; Rats; Vasoconstrictor Agents; Vasopressins

In view of the fact of the high concentration of neuronal nitric oxide synthase (NOS) in the supraoptic and paraventricular nuclei as well as the posterior pituitary, it has been supposed that nitric oxide (NO) may be involved in the regulation of hormone secretion from these sites. In the present study, L-arginine, the precursor of NO, and N(omega)-nitro-L-arginine methyl ester (L-NAME), the NOS inhibitor, were intracerebroventricularly (i.c.v.) administered into the pentobarbital anesthetized rats. The results showed that plasma arginine vasopressin (AVP) concentration increased after the injection of L-arginine (1.0 mg in microliters, i.c.v.) and decreased after the L-NAME (270 micrograms in 5 microliters, i.c.v.). The elevated plasma AVP level in response to short-term hypotension induced by intravenous infusion of sodium nitroprusside was also significantly reduced by i.c.v. administration of L-NAME. The results indicate that NO acts as a stimulating factor to both the basal and reflex release of AVP, opposing the view that NO plays an inhibitory role in the regulation of AVP secretion.

Topics: Anesthesia; Animals; Arginine; Enzyme Inhibitors; Hypotension; Injections, Intraventricular; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Supraoptic Nucleus; Vasopressins

Hypotension during endotoxic shock is related to reduced vascular responsiveness to vasoconstrictors. Neuropeptide Y (NPY) is known to potentiate the pressor response to some agonists, and NPY infusion has been shown to improve hemodynamics and survival in endotoxemic rats. We therefore studied the effect of NPY infusion on the suppressed pressor effect of norepinephrine (NE), angiotensin II (AII), vasopressin (VP), and endothelin (ET) in conscious endotoxemic rats. Chronically cannulated conscious rats were infused with a non-hypotensive dose of endotoxin (LPS, 10 micrograms/10 microliters/min) throughout the experiment. Infusion of NPY, 40 pmol/10 microliters/min was started 15 minutes before the LPS infusion, and continued for 65 minutes. Five minutes after the termination of NPY infusion, increasing agonist doses were administered i.v. to construct dose-response curves. Each experiment included one control group where saline replaced LPS, and one control group where saline replaced NPY. LPS infusion caused suppression of the pressor responses to all four agonists, as expressed by ED50 and by decreased pressor response to the individual agonist doses. In addition, LPS infusion altered the bradycardic response to AII and ET. NPY infusion prior to the administration of NE, AII and VP resulted in partial reversal of the LPS-induced suppressed responsiveness to these agonists. NPY infusion had no effect on the response to ET in either control or endotoxemic rats. Partial reversal of the suppressed responsiveness to the three agonists by NPY infusion may contribute to the observed NPY-induced improvement of blood pressure and survival rate during endotoxic shock.

Topics: Animals; Endothelins; Endotoxins; Hemodynamics; Hypotension; Lipopolysaccharides; Male; Neuropeptide Y; Norepinephrine; Pressoreceptors; Rats; Rats, Wistar; Shock, Septic; Vasopressins

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

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

Hypotensive hemorrhage is a major stimulus for vasopressin (VP) release, but in rats it is uncertain which receptors initiate this response. We have investigated this issue using transient occlusion of the inferior vena cava to simulate hypotensive hemorrhage. Single-unit recording experiments done in the supraoptic nucleus of pentobarbital-anesthetized rats demonstrated that severe caval occlusion, sufficient to drop mean arterial pressure (MAP) below 30 mmHg, excited 88% of putative VP neurosecretory cells and a similar proportion of putative oxytocin (OT) cells. Responsive VP cells increased their firing by 8.5 +/- 0.6 spikes/s within 11.2 +/- 0.8 s of the fall in MAP. This response was unrelated to the size of the fall in MAP and was unchanged by combined sinoaortic denervation (SAD) and vagal denervation, by T1 spinal section, or by administration of the angiotensin-converting enzyme inhibitor captopril, except that spinal section decreased the response latency. Moderate caval occlusion, sufficient to drop MAP to approximately 50 mmHg, did not excite any of the OT cells tested but did excite 65% of VP cells, causing a 3.8 +/- 0.3 spikes/s increase in firing after a delay of 9.0 +/- 1.3 s. This response was proportional to the size of the preceding fall in MAP, and after combined SAD and vagal denervation only 20% of VP cells still responded. Elimination of sinoaortic or vagal afferents alone had no effect on VP cell responses to moderate caval occlusion, except that SAD significantly increased the response latency. These data suggest that in rat the mechanisms that initiate the VP response to hypotensive hemorrhage depend on stimulus intensity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Animals; Blood Pressure; Captopril; Denervation; Electric Stimulation; Hemorrhage; Hypotension; Male; Metaraminol; Rats; Rats, Wistar; Sinoatrial Node; Spinal Cord; Supraoptic Nucleus; Vagus Nerve; Vasopressins

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

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

Neurohypophysectomy (NHX) attenuates the adrenocorticotropic hormone (ACTH) response to arterial hypotension but not corticotropin-releasing hormone (CRH) or insulin-induced hypoglycemia in conscious dogs. The purpose of the present study was to determine if increasing vasopressin (AVP) in the cephalic circulation by carotid infusion normalizes the ACTH response to hypotension attenuated by NHX. Five male, conditioned dogs underwent controlled, acute decreases in arterial pressure (by approximately 25 mmHg) by infusion of sodium nitroprusside (NP) before and > 4 wk after selective NHX. ACTH increased from 40 +/- 3 to 242 +/- 79 pg/ml during NP in the intact state. This response was greatly attenuated after NHX (peak ACTH 81 +/- 15 pg/ml). Simultaneous intravenous infusion of AVP (12.5 ng/min) had a small, augmenting effect on the ACTH response to NP (peak ACTH 120 +/- 27 pg/ml). Intracarotid AVP (12.5 ng/min) greatly augmented the ACTH response to NP (peak ACTH 202 +/- 26 pg/ml) such that it was no longer different from the intact response. Neither intravenous nor intracarotid AVP infusion per se had a great effect on ACTH. A normal ACTH response to hypotension requires an intact neurohypophysis and is mediated by a cephalic action of magnocellular AVP.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Carotid Arteries; Dogs; Heart Rate; Hypophysectomy; Hypotension; Infusions, Intravenous; Injections, Intra-Arterial; Male; Nitroprusside; Pituitary Gland, Posterior; Vasopressins

Vasopressin may be associated with systemic hemodynamic changes, including severe myocardial ischemia, even in healthy patients. A 36-year-old woman underwent laparoscopy for the treatment of a uterine leiomyoma. After intravascular injection of vasopressin, she experienced life-threatening hypotension, and the procedure was subsequently aborted. After she recovered, she underwent successful laparoscopy without the use of vasopressin, and no complications occurred. As endogenous vasopressin levels sometimes rise during laparoscopy, patients may become susceptible to the drug's effects, and appropriate precautions must be taken.

Topics: Adult; Blood Pressure; Bradycardia; Female; Follow-Up Studies; Hemostatics; Humans; Hypotension; Injections; Intraoperative Complications; Laparoscopy; Leiomyoma; Reoperation; Uterine Neoplasms; Vasoconstrictor Agents; Vasopressins

In animals subjected to hemorrhage, plasma arginine vasopressin concentrations increase to levels sufficient to cause vasoconstriction, thus attenuating the hypotensive response. The purpose of this study was to examine the contribution of vasopressin to blood pressure regulation during hypotension in humans. Hypotension was induced in twelve normal subjects by lower body negative pressure (LBNP) before and after intravenous administration of vasopressin V1 receptor antagonist. Before drug administration, LBNP reduced systolic blood pressure from 125 +/- 4 to 78 +/- 12 mmHg (P < 0.01) as vasopressin concentration increased from 2.9 +/- 0.6 to 17 +/- 6 pg/ml (P < 0.05). After administration of the vasopressin antagonist, LBNP reduced systolic blood pressure from 128 +/- 3 to 89 +/- 11 mmHg (P < 0.01). The hypotensive response to LBNP was not potentiated by inhibiting vasopressin's vasoconstrictive effects (P = NS). Thus hypotension causes marked increases in plasma vasopressin concentration. In contrast to findings in animal studies, however, vasopressin does not contribute to the maintenance of blood pressure during hypotension in humans.

Topics: Adult; Antidiuretic Hormone Receptor Antagonists; Blood Pressure; Female; Hemodynamics; Humans; Hypotension; Lower Body Negative Pressure; Male; Pressoreceptors; Vasopressins

The effects of iso- and hypo-osmotic reduction of the CSF [Na+] on the tolerance to blood loss and concomitant cardiovascular and humoral responses were studied in conscious sheep. Animals only subjected to haemorrhage served as controls. The changes in CSF composition were induced by intracerebroventricular infusions of 0.3 M mannitol, respectively, 0.04 M NaCl. In the former instance the CSF [Na+] was reduced by 18 mM whereas a lowering by 13 mM concomitant with decreased CSF osmolality (mean change 25 mOsm kg-1) was seen in response to the NaCl solution. Apart from a slight lowering of the cardiac output during the infusion of 0.3 M mannitol preceding haemorrhage, the changes in CSF composition did not have any significant haemodynamic effects in the normovolaemic animal, or altered the cardiovascular responses to a subsequent hypotensive haemorrhage. The amount of blood needed to be withdrawn to obtain the predefined degree of hypotension did not differ significantly between treatment groups. The plasma vasopressin and angiotensin II concentrations were consistently increased by the hypotensive haemorrhage, but the magnitude of the vasopressin response was significantly reduced when the CSF [Na+] was lowered. We conclude that lowered CSF [Na+] and/or osmolality, in contrast to increased CSF [Na+], does not influence the tolerance to blood loss or the accompanying haemodynamic changes in sheep, in spite of an attenuated vasopressin response.

Topics: Angiotensin II; Animals; Consciousness; Female; Hemodynamics; Hemorrhage; Hypotension; Injections, Intraventricular; Mannitol; Osmolar Concentration; Potassium; Renin; Sheep; Sodium; Sodium Chloride; Vasopressins

We examined the effect of acute hypotensive hemorrhage on corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) messenger RNAs (mRNAs) in neurons of the rat hypothalamus. Sprague-Dawley male rats were cannulated (femoral artery and vein) and received a 15 ml/kg.3 min hemorrhage on the morning of the fourth day. Time controls received no hemorrhage. After light halothane anesthesia, the rats were decapitated at 1 or 4 h (six to nine rats per group). The hypothalami were removed, frozen, and sectioned at 12 microns. In situ hybridization was performed using two 48-base oligodeoxynucleotide probes for CRH and AVP message, respectively. Hemorrhage led to a fall in arterial blood pressure and heart rate that recovered by 1 h. Plasma ACTH, corticosterone, and AVP were elevated 20, 60, and 90 min after hemorrhage, but returned to near control levels by 4 h. CRH mRNA was significantly elevated 1 and 4 h after hemorrhage, as compared to time controls, in parvocellular neurons of the paraventricular nuclei. However, AVP mRNA was not different from controls at 1 or 4 h after hemorrhage in the magnocellular or parvocellular paraventricular nuclei, or in the supraoptic or accessory nuclei of the hypothalamus. AVP mRNA was also found in neurons of the suprachiasmatic nuclei, but there was no difference in the amount of mRNA between the 1-h hemorrhage and control groups. These data suggest that neural signals, originating for cardiovascular receptors activated by hemorrhage, up-regulate message for CRH but not for AVP in the paraventricular nuclei of the rat hypothalamus.

Topics: Adrenocorticotropic Hormone; Animals; Arginine Vasopressin; Corticosterone; Corticotropin-Releasing Hormone; Hemorrhage; Hypotension; Hypothalamus; Male; Rats; Rats, Inbred Strains; Receptors, Cell Surface; RNA, Messenger; Vasopressins

Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Angiotensin II; Animals; Dogs; Female; Glucocorticoids; Hypotension; Male; Nitroprusside; Reflex; Renin; Saralasin; Vasopressins; Water Deprivation

To investigate whether activation of afferent and central baroreceptor pathways could differentiate between pure autonomic failure (PAF) and multiple system atrophy with autonomic failure (MSA), we determined the effect of upright tilt on circulating levels of vasopressin in patients with PAF and patients with MSA. We also studied 14 normal subjects, nine of whom developed acute hypotension due to vasovagal syncope. In patients with PAF and in normal subjects with vasovagal syncope, upright tilt induced marked hypotension and a pronounced increase in the plasma concentration of vasopressin (1.1 +/- 0.3 to 38.0 +/- 8.0 pmol/l in PAF and 1.0 +/- 0.2 to 27.4 +/- 7.2 pmol/l in vasovagal syncope, p less than 0.005 for both). In patients with MSA, upright tilt also elicited profound hypotension but circulating levels of vasopressin increased little (0.5 +/- 0.1 to 1.5 +/- 0.3 pmol/l, p less than 0.05). During upright tilt, the plasma concentration of norepinephrine significantly increased in normal subjects but did not increase in patients with autonomic failure. Our results indicate that afferent and central baroreceptor pathways involved in vasopressin release are normal in patients with PAF but are impaired in patients with MSA. Thus, measurement of baroreceptor-mediated vasopressin release appears to provide a clear marker to differentiate between patients with PAF and patients with MSA.

Topics: Adult; Aged; Autonomic Nervous System Diseases; Female; Humans; Hypotension; Male; Middle Aged; Multiple Organ Failure; Vasopressins

Of 191 patients with birthweight less than 1500 gm admitted to our neonatal intensive care unit in a 2-year period, 41 underwent cardiopulmonary resuscitation (CPR). Eleven of 41 very low birthweight (VLBW) (27%) survived to be discharged. None of the infants who received CPR after 72 hours of life survived. Also, all infants who underwent CPR, both in the delivery room and neonatal intensive care unit (NICU), died. The most significant factor distinguishing survivors from nonsurvivors was the demonstration of vasopressor unresponsive hypotension 20 hours prior to CPR in the latter group. This study confirmed the very poor survival rate after CPR in VLBW infants. We conclude that performance of CPR in patients with vasopressor unresponsive hypotension or previous delivery room resuscitation should be considered a rescue or experimental treatment and parents should be given the option of no resuscitation. Future research efforts should be directed to better the understanding and treatment of cardiovascular dysfunction prior to cardiac arrest.

Topics: Cardiopulmonary Resuscitation; Delivery Rooms; Humans; Hypotension; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Retrospective Studies; Survival Rate; Time Factors; Treatment Outcome; Vasopressins

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

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

The effect of elevated cerebrospinal fluid Na+ concentration (CSF [Na+]) on the tolerance of blood loss, and concomitant cardiovascular and humoral responses were studied in conscious sheep. A slow (0.7 ml kg-1 min-1) venous haemorrhage was continued until the mean systemic arterial pressure suddenly decreased to less than 50 mmHg, or in the absence of hypotension, until a total blood loss of 25 ml kg-1. Significantly more blood had to be removed to induce hypotension in animals receiving an intracerebroventricular (i.c.v.) infusion (0.02 ml min-1) of 0.5 M NaCl (starting 30 min before haemorrhage and continued throughout the experiment) compared to control haemorrhages without concomitant i.c.v. infusion (22.7 +/- 1.2 ml vs 16.9 +/- 0.9 ml kg-1). In one animal, subjected to 0.5 M NaCl infusion, the blood pressure was still maintained at 25 ml kg-1 of haemorrhage. In spite of a larger blood loss, animals receiving i.c.v. infusion of hypertonic NaCl had an improved recovery of the blood pressure after haemorrhage, due to a better maintained cardiac output rather than to a reinforced increase of the vascular resistance. The improved cardiovascular responses to haemorrhage during elevated CSF [Na+] are not readily explained by the effects on the plasma concentrations of vasopressin, angiotensin II or noradrenaline, although the latter was augmented. The plasma protein concentration decreased already during the 30 min of hypertonic NaCl infusion preceding haemorrhage, and the haemodilution caused by the subsequent blood removal was aggravated, which indicates that this treatment also causes transfer of fluid to the plasma compartment. We conclude that elevated CSF [Na+] increases tolerance to haemorrhage and improves cardiovascular function after blood loss in sheep. Since the haemodynamic responses in many respects were similar to those reported in response to the systemic administration of a small volume of hypertonic NaCl solution in haemorrhagic shock, part of the effect of that treatment may be mediated via cerebral effects of increased Na+ concentration.

Topics: Angiotensin II; Animals; Female; Hemodynamics; Hemorrhage; Hypotension; Injections, Intraventricular; Norepinephrine; Saline Solution, Hypertonic; Sheep; Shock, Hemorrhagic; Vasopressins

Factors from the neurohypophysis are important in the control of anterior pituitary function. This study evaluated the hypothesis that the neurophypophysis is an integral component of the adrenocorticotropin (ACTH) response to certain stimuli. Furthermore, we investigated the possibility that the importance of the neurohypophysis during corticotropic stimuli can be classified by the magnitude of the systemic vasopressin response induced. The ACTH response to insulin-induced hypoglycemia (INS), nitroprusside hypotension (NP), or ovine corticotropin-releasing factor (CRF) infusion (20 ng/kg/min) was measured in dogs before (intact) and greater than 2 weeks after selective transbuccal neurohypophysectomy (NHX). INS (0.2 U/kg) resulted in a significant decrease in plasma glucose from 93 +/- 1 to 33 +/- 2 mg/dl at 30 min and a significant increase in plasma ACTH from 53 +/- 10 to 306 +/- 33 pg/ml in intact dogs whereas the vasopressin (AVP) response was small (2.8 +/- 0.3 to 5.5 +/- 0.7 pg/ml). NHX had no effect on the blood glucose or ACTH response to INS. NP resulted in large increases in ACTH from 54 +/- 8 to 351 +/- 89 pg/ml and in AVP from 2.7 +/- 0.2 to 272 +/- 98 pg/ml. In contrast to INS, NHX significantly attenuated the ACTH and AVP responses to NP. The ACTH response to CRF was not attenuated by NHX, indicating normal pituitary corticotropic function. In summary, NHX attenuated the ACTH response to hypotension (large peripheral AVP response) but not to INS or CRF (small peripheral AVP response).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Animals; Blood; Blood Glucose; Corticotropin-Releasing Hormone; Dogs; Hydrocortisone; Hypoglycemia; Hypophysectomy; Hypotension; Insulin; Male; Nitroprusside; Osmolar Concentration; Potassium; Sodium; Vasopressins

In order to assess the effects of age on blood pressure, pulse, and neurohumoral responses to hypotensive stress, we infused nitroprusside into healthy young and old men until mean arterial blood pressure was reduced 20% from basal. Elderly subjects were much more sensitive to nitroprusside. Pulse increases in response to this hypotensive stress were markedly reduced in the elderly, but renin, vasopressin, and norepinephrine responses were not different between young and old. We conclude that cardioacceleration, one of the primary defenses against hypotension, is impaired with age. However, neurohumoral responses to hypotension are intact in the elderly.

Topics: Adult; Aged; Aging; Blood Pressure; Humans; Hypotension; Male; Middle Aged; Neurotransmitter Agents; Nitroprusside; Norepinephrine; Pulse; Renin; Vasopressins

The effects of Eschericia coli endotoxin on vascular responsiveness were compared with those of sodium nitroprusside in pithed rats. Infusion of endotoxin (250 micrograms kg-1 h-1) produced a fall in mean arterial blood pressure (11 mmHg) and impaired vasodepressor responses to endothelin, 5-hydroxytryptamine, acetylcholine, bradykinin, sodium nitroprusside and salbutamol. Prevention of endotoxin-induced hypotension with vasopressin infusion (0.64 i.u. kg-1 h-1 i.v.) restored responsiveness to bradykinin, tended to restore responsiveness to endothelin and sodium nitroprusside but failed to restore responsiveness to acetylcholine, 5-HT or salbutamol. Infusion of sodium nitroprusside at a rate (400 micrograms kg-1 h-1) producing a similar fall in blood pressure to that produced by endotoxin markedly impaired vasodepressor responsiveness to 5-HT. However, this was fully restored when the hypotension was prevented by vasopressin infusion. Vasodepressor responsiveness to either acetylcholine or salbutamol was not impaired by sodium nitroprusside in vasopressin-infused rats. The impairment of vasodepressor responsiveness by endotoxin is not due to endotoxin-induced hypotension and does not fit clearly with an endotoxin-mediated impairment of endothelial function.

Topics: Acetylcholine; Animals; Blood Pressure; Bradykinin; Endothelins; Endothelium, Vascular; Endotoxins; Escherichia coli; Hypotension; Male; Nitroprusside; Rats; Rats, Inbred Strains; Serotonin; Vasopressins

This study investigated possible mechanisms for the hypotension produced by nitroprusside infusion in conscious dogs pretreated with a V1 vasopressin antagonist. The hypothesis that an action of vasopressin at V2-like receptors contributes to the hypotension was tested by comparing the effects of a V1 antagonist to the effects of a combined V1/V2 antagonist. Nitroprusside infusion produced dose-dependent decreases in arterial and atrial pressures. Larger decreases in pressures were produced in animals pretreated with either antagonist; however, the decreases in V1/V2-blocked dogs were not less than the decreases in V1-blocked dogs. These data suggest that V2-like actions of vasopressin do not contribute to the hypotensive effects of V1 blockade. A second hypothesis was that the greater hypotension was due to activation of a cardiac reflex to cause withdrawal of sympathetic tone, a decrease in peripheral resistance, and adrenal activation. Measurement of cardiac output revealed that the larger decreases in arterial pressure were due to larger decreases in total peripheral resistance. The hypotension was also associated with decreases in heart rate, unchanging plasma norepinephrine concentration, and increases in epinephrine concentration. These data are consistent with the hypothesis that the fall in pressure observed in dogs pretreated with a V1 antagonist is secondary to a decrease in peripheral resistance that is due at least in part to withdrawal of sympathetic tone.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Cardiac Output; Deamino Arginine Vasopressin; Dogs; Dose-Response Relationship, Drug; Epinephrine; Female; Heart Rate; Hypotension; Injections, Intravenous; Male; Nitroprusside; Norepinephrine; Receptors, Angiotensin; Receptors, Vasopressin; Sympathetic Nervous System; Vascular Resistance; Vasopressins

In order to investigate the physiological role of angiotensin II (ANG II) in the control of vasopressin (VP) secretion, the VP responses to hypotension induced by hemorrhage (20 ml/kg, n = 10) or nitroprusside infusion (1-10 micrograms/kg.min, n = 9) were studied with or without blockade of ANG II formation by the converting enzyme inhibitor captopril in conscious rabbits. Administration of captopril (5 mg/kg, iv) caused a small decrease in mean arterial pressure but did not enhance the hypotensive response to subsequent hemorrhage or nitroprusside infusion. The renin response to both stimuli was enhanced by captopril, whereas the increase in plasma ANG II concentration was attenuated. Plasma VP (PAVP) concentration increased during hemorrhage (2.0 +/- 0.2-113.6 +/- 47.7 pg/ml, P less than 0.01) and nitroprusside infusion (2.1 +/- 0.3-5.1 +/- 1.0 pg/ml, P less than 0.01). Captopril did not change basal plasma PAVP, nor did it attenuate the VP responses to hemorrhage or nitroprusside. Indeed, captopril tended to enhance the VP responses to hemorrhage (2.3 +/- 0.3-147.1 +/- 65.9 pg/ml) and nitroprusside infusion (1.9 +/- 0.2-15.4 +/- 6.0 pg/ml). The relationship between log PAVP and mean arterial pressure during hemorrhage and nitroprusside infusion in the presence of captopril was not different than in the absence of captopril. These results indicate that in conscious rabbits, the renin-angiotensin system does not contribute to the increase in VP secretion during hypotension induced by hemorrhage or nitroprusside infusion.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Heart Rate; Hemorrhage; Hypotension; Male; Nitroprusside; Rabbits; Reference Values; Vasopressins

To clarify the mechanism of postprandial hypotension (PPH), we made microneurographic analyses of patients with PPH and 10 healthy controls by recording multi-unit vasoconstrictive impulses of muscle sympathetic nerve activity (MSNA) directly from the tibial nerve fascicles during a glucose tolerance test. Oral intake of 75 grams glucose in 225 ml of water produced significant and prolonged hypotension in all patients and an increase in MSNA in all healthy subjects. Insulin and glucose responses were not significantly correlated with arterial blood pressure reduction. PPH was prevented by an infusion of vasopressin (0.3 U/min) given before glucose intake. These results suggest that PPH is caused by the lack of sympathetic compensation for the systemic hypotensive stress of splanchnic blood pooling that occurs after food ingestion, and that prior treatment with vasopressin reduces the portal venous flow by constricting the splanchnic vessels in patients with PPH.

Topics: Adult; Aged; Analysis of Variance; Blood Pressure; Eating; Female; Glucose Tolerance Test; Heart Rate; Humans; Hypotension; Male; Middle Aged; Reference Values; Sympathetic Nervous System; Tibial Nerve; Vasopressins

Extracellular norepinephrine (NE) levels in the paraventricular/anterior hypothalamic area (P/A) and in the dorsomedial medulla (DM) in conscious Sprague-Dawley rats were estimated by in vivo microdialysis before, during, and after sustained hypotension (75 mmHg mean arterial pressure) produced either by hemorrhage (Hem) or by 2-chloroadenosine infusion (2-Cl-ADO, 2.6-26.0 micrograms/min iv). P/A and DM NE were also measured before, during, and after hypertonic saline infusion (HTS; 1.5 M NaCl at 10 microliters.100 g-1.min-1 iv). P/A and DM NE increased during both Hem and 2-Cl-ADO and returned to baseline after reinfusion of hemorrhaged blood or after 2-Cl-ADO was stopped. However, Hem caused greater increases in P/A NE than 2-Cl-ADO despite equivalent decreases in blood pressure. Hem and 2-Cl-ADO produced equivalent changes in DM NE. HTS did not change P/A or DM NE despite increases in blood pressure of approximately 15 mmHg and plasma osmolality of approximately 30 mosmol/kgH2O. We conclude that 1) hypotension increases P/A and DM NE, which may mediate compensatory responses, 2) Hem is a more potent stimulus for NE release in the P/A than isovolemic hypotension induced by 2-Cl-ADO, and 3) the hypertensive response to HTS does not involve changes in P/A or DM NE.

Topics: 2-Chloroadenosine; Animals; Blood Pressure; Central Nervous System; Consciousness; Hemorrhage; Hypotension; Male; Medulla Oblongata; Norepinephrine; Osmolar Concentration; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Vasopressins

SK&F 101926, a synthetic peptide, is a potent antagonist of vasopressin at both the V2 and the V1 receptors. Following intravenous administration of SK&F 101926 (5 mg/kg), mean arterial pressure (MAP) immediately fell 75 mm Hg. Heart rate increased approximately 50 beats/min. Cutaneous flushing and cyanosis appeared approximately 2 to 5 min after the SK&F 101926 administration. Three of the five rats died within 40 min with no improvement in either color or MAP. The two surviving animals slowly recovered from these symptoms. The hypotension and flushing recorded in these studies resembled the effects during hypotensive shock. SK&F 101926 degranulated rat peritoneal mast cells in vitro as measured by the liberation of histamine. Analogs of SK&F 101926 were identified having reduced activity to release histamine from mast cells in vitro. The activity of these analogs to release histamine in vivo was also tested, as reflected by rat paw edema. A positive correlation was found between the potency to produce edema in vivo and the potency to release mast cell histamine in vitro (r = 0.94, p less than 0.05). In addition, compounds that released mast cell histamine and induced rat paw edema also produced hypotension and death when administered intravenously, while analogs which produced minimal histamine release in vitro produced minimal or no cardiovascular changes or lethality in vivo at the same dosages (5 mg/kg). Finally, cyproheptadine (10 mg/kg), an antagonist at both the serotonin and the histamine receptors, blunted the effects of SK&F 101926 on MAP and blocked the lethality. Pretreatment with a combination of histamine (H1 and H2) antagonists provided little protection against the SK&F 101926-induced toxicity. These data indicate that the cardiovascular toxicity of SK&F 101926 (and related peptides) is mediated via the release of autocoids from mast cells. Serotonin appears to play a major role in mediating the cardiovascular toxicity of SK&F 101926.

Topics: Animals; Arginine Vasopressin; Cell Degranulation; Edema; Hindlimb; Histamine Release; Hypotension; Male; Mast Cells; Rats; Rats, Inbred Strains; Time Factors; Vasopressins

To evaluate whether, and to what extent, release of endogenous vasopressin supports blood pressure when efferent sympathetic drive is blocked by epidural anesthesia, the authors studied the effects of high epidural anesthesia alone and when vasopressin was prevented from acting at its vascular (V1)-receptor in six awake, trained, unsedated dogs. On different days, the same dose of 0.5% bupivacaine (8-13 ml) was injected epidurally in a randomized fashion either in the presence or absence of (V1)-vasopressin receptor blockade, and the effects were evaluated on cardiovascular (arterial blood pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, and on plasma concentrations of vasopressin and renin. Results were also contrasted to those obtained after epidural injection of saline alone (placebo) in the same dogs. When endogenous vasopressin was prevented from acting by intravenous pretreatment with a specific V1-receptor antagonist (beta-mercapto-beta, beta-cyclopenta-methylene-propionyl-O-Me-Tyr-Arg-Vasopressin), epidural anesthesia resulted in a rapid and sustained 35% decrease in mean arterial blood pressure from 92 mmHg +/- 5 SE to 60 mmHg +/- 4. In contrast, only a 14% decrease in mean blood pressure from 92 mmHg +/- 5 to 79 mm Hg +/- 6 was noted after epidural anesthesia alone. This difference between groups was statistically significant (P = 0.0001). The V1-receptor blockade alone had no detectable effect. Vasopressin plasma concentrations significantly increased from 3.4 +/- 0.3 pg.ml-1 to 16.2 +/- 3.2 pg.ml-1 after epidural anesthesia but did not change after epidural saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia, Epidural; Animals; Blood Pressure; Bupivacaine; Dogs; Heart Rate; Hypotension; Renin; Vasopressins

The interaction between vasopressinergic and prostanoid mechanisms in the control of cerebral hemodynamics in the conscious hypotensive newborn pig was investigated. Indomethacin treatment (5 mg/kg) of hypotensive piglets caused a significant decrease in blood flow to all brain regions within 20 min. This decrease in cerebral blood flow resulted from increased cerebral vascular resistances of 52 and 198% 20 and 40 min after treatment, respectively. Cerebral oxygen consumption was reduced from 2.58 +/- 0.32 ml.100 g-1.min-1 to 1.01 +/- 0.12 and 0.29 +/- 0.08 ml.100 g-1.min-1 20 and 40 min after indomethacin, respectively, in hemorrhaged piglets. Treatment with the putative vascular (V1) receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid-2-(O-methyl)tyrosine]arginine vasopressin (MEAVP) had no effect on regional cerebral blood flow, calculated cerebral vascular resistance, or cerebral metabolic rate either before or during hemorrhagic hypotension. However, decreases in cerebral blood flow and metabolic rate and increases in vascular resistance on treatment with indomethacin were blunted markedly in animals treated with MEAVP. These data are consistent with the hypothesis that the prostanoid system contributes to the maintenance of cerebral blood flow and cerebral metabolic rate during hypotension in the newborn pig, as reported previously, and implicate removal of vasopressinergic modulation by prostanoids as a potential mechanism for indomethacin-induced cerebral vasoconstriction in hypotensive newborn piglets.

Topics: Animals; Animals, Newborn; Arginine Vasopressin; Biomechanical Phenomena; Blood Pressure; Cardiac Output; Cerebrovascular Circulation; Hemorrhage; Hypotension; Indomethacin; Lypressin; Oxygen Consumption; Prostaglandins; Swine; Vascular Resistance; Vasopressins

The aim of this paper was to study plasma atrial natriuretic factor, renin activity, aldosterone and antidiuretic hormone in low-output heart failure syndromes such as cardiogenic shock, hypovolemic shock and hypotension with bradycardia syndrome. A total of 30 patients were investigated: 10 with cardiogenic shock due to acute myocardial infarction of the anterior wall (systolic and diastolic blood pressure 56.0 +/- 3.7/40.5 +/- 2.0 mmHg; heart rate 119.7 +/- 1.2 beats/min; central venous pressure 16.2 +/- 0.6 cmH2O) (I group), 10 with hypovolemic shock induced by melena in peptic ulcer (systolic and diastolic blood pressure 74.5 +/- 1.5/57.5 +/- 1.7 mmHg; heart rate 111.0 +/- 1.4; central venous pressure 6.3 +/- 0.5 cmH2O) (II group), 10 with hypotension with bradycardia syndrome which occurred in patients during acute myocardial infarction of the inferior wall (systolic and diastolic blood pressure 71.9 +/- 2.0/58.0 +/- 2.6 mmHg; heart rate 52.0 +/- 2.2 beats/min; central venous pressure 4.6 +/- 0.4 cmH2O) (III group). Plasma atrial natriuretic factor values were measured using radioimmunoassay after chromatographic pre-extraction; plasma renin activity, aldosterone and antidiuretic hormone values were calculated using radioimmunoassay. Circulating atrial natriuretic factor was significantly (p less than 0.01) higher in patients with cardiogenic shock (102.4 +/- 7.4 pg/ml) than in healthy volunteers (8.4 +/- 0.3 pg/ml). In the former there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the IInd and IIIrd groups of patients were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Bradycardia; Cardiac Output, Low; Female; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Myocardial Infarction; Renin; Shock; Shock, Cardiogenic; Vasopressins

We investigated whether a reflex increase in plasma vasopressin level due to hemorrhagic hypotension affects brain blood flow. In 60 lightly anesthetized, artificially ventilated rats, the flow was determined with radiolabeled microspheres. We found excellent maintenance of blood flow throughout all brain regions during the hypotensive state (71 mmHg on average), and such maintenance of flow was not modulated at all by a supramaximal intravenous dose of the selective vasopressin V1-receptor antagonist [d(CH2)5 Tyr-(Me)]AVP. The latter finding also implies that the V1 antagonist failed to unmask the vasodilator type actions of V2 receptors on the maintenance of flow during hemorrhagic hypotension. These were true also when the cervical sympathetic bundles were severed bilaterally. The plasma level of endogenous vasopressin was increased during hypotension, ranging from 118 to 973 pg/ml. Despite this increase, the brain blood flow was entirely independent of the plasma vasopressin level in all the brain regions studied. We conclude that the brain circulation of rats can maintain its blood flow during hemorrhagic hypotension without any apparent contribution from a concomitant reflex increase in plasma vasopressin. Despite our negative results for the brain blood flow, the possible segmental effects of circulating vasopressin on the brain arterial caliber remain to be clarified under conditions of hemorrhagic hypotension.

Topics: Animals; Cerebral Hemorrhage; Cerebrovascular Circulation; Hypotension; Male; Microspheres; Osmolar Concentration; Rats; Rats, Inbred Strains; Reference Values; Vasopressins

The circulating levels of vasopressin, catecholamines and renin activity before, during and following a 10-20% fall in mean arterial blood pressure induced by sodium nitroprusside were measured in six chronically catheterized lambs during the first week of life. No significant changes in pHa, PaO2, PaCO2, Plasma sodium or osmolality were observed during or following the infusion of sodium nitroprusside at an average of 12 g.kg-1.min-1 (table I). However, the fall in blood pressure at the end of 60 minutes infusion, was associated with significant increases in the plasma levels of vasopressin from a control value of 2.4 +/- 0.57 to a maximum of 35.1 +/- 16.3 pg/ml (p = .002), renin activity from 6.7 +/- 1.56 to 27.4 +/- 11.44 ng.ml-1.hr-1 (p = .003), and catecholamines from 189.3 +/- 42.15 to 543.3 +/- 100.52 pg.ml-1 (p = .0001). The increase in vasopressin is lower, while that of PRA was higher and catecholamines similar to those found in the ewe. Plasma renin activity (PRA) and catecholamine levels remained elevated for at least 30 minutes following the end of the infusion while the mean blood pressure rose significantly above control levels and remained elevated for twenty minutes. We speculate that the persistent elevated levels of vasoactive mediators are responsible for the prolonged rebound hypertension following the cessation of the nitroprusside infusion and is the result of an immaturity of either a feedback process or metabolism of the vasoactive mediators or a combination of both mechanisms. This rebound hypertension could have adverse effects particularly in the very immature neonate.

Topics: Animals; Animals, Newborn; Blood Pressure; Catecholamines; Disease Models, Animal; Ferricyanides; Heart Rate; Hypotension; Nitroprusside; Renin; Renin-Angiotensin System; Sheep; Vasopressins

The extent to which age influences the effect of prolonged intravenous infusion and withdrawal of arginine vasopressin (AVP) on blood pressure was investigated in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY) of 6-, 10-, 14-, 18-, and 22-week age groups. The pressor response to AVP (20 ng/kg/min for 3 hours) was relatively well maintained in WKY but showed an age-dependent tachyphylaxis in SHR. After cessation of the infusion, arterial pressure of SHR fell in all age groups. In contrast, withdrawal of AVP in WKY resulted in little or no hypotensive response. Thus, a withdrawal-induced antihypertensive phenomenon (WAP) to AVP was specific to SHR. The magnitude of the WAP was significantly correlated with the level of initial blood pressure in SHR (r = -0.81, p less than 0.001). The magnitude of the tachyphylaxis during the AVP infusion was also correlated with the level of initial blood pressure in SHR (r = -0.66, p less than 0.001). Accordingly, a significant correlation was found between the magnitude of the WAP and the degree of tachyphylaxis to the pressor activity of AVP in SHR (r = 0.69, p less than 0.001). The significance of this is unknown, but it might mean that a common underlying mechanism existed in the expression of the tachyphylactic phenomenon and the WAP in SHR. Finally, an apparent enhancement in the baroreceptor reflex sensitivity was observed in both SHR and WKY during the infusion of AVP, but the magnitude of this enhancement appeared to be greater in SHR than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Heart Rate; Hypotension; Pressoreceptors; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reflex; Tachyphylaxis; Time Factors; Vasopressins

Discrete brain structures were analysed for gamma-aminobutyric acid (GABA) and vasopressin content in normo- and hypotensive rats treated with the glutamic acid decarboxylase inhibitor, 3-mercaptopropionic acid (MPA) and the GABAA agonist muscimol. In the normotensive group treated with MPA only, the concentration of vasopressin increased in the supraoptic nucleus, indicating an inhibitory role for GABA. In the hypotensive group a rise in the vasopressin level in the nucleus of the solitary tract was detected and the GABA level decreased in the supraoptic nucleus. Muscimol decreased the concentration of vasopressin in the nucleus of the solitary tract. The changes in the concentration of vasopressin may be a result of increased or decreased activation of the GABAergic system. The results show that the GABA- and vasopressinergic systems somehow interact although the more precise way of action remains to be clarified.

Topics: 3-Mercaptopropionic Acid; Animals; Brain; Enzyme Inhibitors; gamma-Aminobutyric Acid; Hypotension; Male; Muscimol; Rats; Rats, Inbred Lew; Sulfhydryl Compounds; Vasopressins

In patients with congestive heart failure, atrial natriuretic factor may serve as a counter-regulatory hormone, offsetting the vasoconstrictive and volume-retentive effects of the sympathetic nervous system, the renin-angiotensin-aldosterone system and vasopressin. Indeed, the plasma levels of atrial natriuretic factor and the vasoconstrictor hormones are often simultaneously elevated in these patients. It is not known, however, whether atrial natriuretic factor remains responsive to sudden reductions in atrial pressure in patients with chronic heart failure, or is unresponsive like the vasoconstrictor systems. To examine this issue, the plasma concentrations of atrial natriuretic factor and the vasoconstrictor hormones were measured in 20 normal subjects and 12 patients with chronic congestive heart failure during incremental lower body negative pressure, an intervention that lowers atrial pressure. In the normal subjects, incremental lower body negative pressure at -10, -20 and -40 mm Hg decreased central venous pressure and pulse pressure. At maximal lower body negative pressure, plasma atrial natriuretic factor levels decreased from 51 +/- 5 to 27 +/- 3 pg/ml (p less than 0.01), whereas increases occurred in plasma levels of norepinephrine (194 +/- 11 to 385 +/- 70 pg/ml, p less than 0.01), renin activity (1.4 +/- 0.2 to 3.9 +/- 0.1 ng/ml per h, p less than 0.01) and vasopressin (1.3 +/- 0.1 to 6.4 +/- 2.4 pg/ml, p less than 0.05). In the patients with congestive heart failure, lower body negative pressure also reduced central venous pressure. Baseline plasma atrial natriuretic factor levels were markedly elevated, averaging 438 +/- 138 pg/ml, and decreased to 317 +/- 87 pg/ml at maximal lower body negative pressure (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Failure; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Renin; Vasopressins

The release of vasopressin, renin, and catecholamines by the fetus during either maternal or fetal hypotension was examined in chronically catheterized fetal lambs. Nitroprusside was infused intravenously for 1 h into seven pregnant ewes (maternal hypotension) or nine fetal lambs (fetal hypotension); the rates were adjusted to achieve a 15 to 30% decrease in mean blood pressure. During maternal hypotension, mean +/- SE vasopressin in maternal plasma increased from 1.2 +/- 0.2 pg.ml-1 to 208 +/- 153 pg.ml-1 and plasma renin activity increased from 1.5 +/- 0.3 ng.ml-1.h-1 to 6.6 +/- 1.6 ng.ml-1.h-1. Fetal vasopressin and plasma renin activity also increased during the same interval from 1.1 +/- 0.3 to 16.9 +/- 7.5 pg.ml-1 and 3.7 +/- 1.1 to 10.5 +/- 2.85 ng.ml-1.h-1, respectively; but no changes were observed in fetal blood pressure, heart rate, or acid base status. During fetal hypotension, mean vasopressin in fetal plasma increased from 4.3 +/- 3.4 pg.ml-1 to 1054 +/- 772 pg.ml-1, plasma renin activity increased from 5.7 +/- 2.2 ng.ml-1 to 22.2 +/- 7.1 ng.ml-1.h-1, and total catecholamines from 174 +/- 58 pg.ml-1 to 810 +/- 416 pg.ml-1. There was no change in fetal heart rate, acid base status, osmolality, or sodium concentration. The fetus became and remained hypertensive for at least 1 h after the end of infusion. This prolonged hypertension was associated with elevated levels of vasopressin and plasma renin activity. Peak vasopressin levels were proportional to the total nitroprusside dose in both the ewe and fetus (maternal r = 0.796, fetus r = 0.870).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Catecholamines; Epinephrine; Female; Ferricyanides; Fetal Blood; Hypotension; Kinetics; Nitroprusside; Norepinephrine; Pregnancy; Renin; Sheep; Vasopressins

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Glomerular Filtration Rate; Heart Failure; Humans; Hyponatremia; Hypotension; Renin-Angiotensin System; Risk Factors; Vasopressins

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Goats; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Pregnancy; Pregnancy Complications, Cardiovascular; Respiration; Vasopressins

Previous investigators have shown that hypotension will cause an increase in plasma levels of both vasopressin and angiotensin II. Significant increases in peripheral resistance after thermal trauma suggested that a similar increase in plasma vasopressin and angiotensin II levels might occur under this condition. This possibility has been studied in the pentobarbital anesthetized dog. Peripheral resistance was calculated from measured cardiac output and mean arterial blood pressure. Vasopressin and angiotensin II levels were measured by radio-immunoassay. The results of this study showed that vasopressin plasma levels increase 4 to 6 fold 15 minutes after thermal trauma and remained elevated (3 to 4 fold) for at least 6 hours. Angiotensin II increased in a linear manner from 15 minutes to 6 hours post trauma. At 6 hours post trauma angiotensin II plasma levels were 4 times pretrauma levels. For the first 4 hours post trauma there was a positive correlation between the sum of vasopressin and angiotensin II plasma levels and the increase in peripheral resistance. These results suggest that the trauma induced increase in peripheral resistance is due to increases in plasma vasopressin and angiotensin II.

Topics: Angiotensin II; Animals; Burns; Cardiac Output; Dogs; Hypotension; Radioimmunoassay; Vascular Resistance; Vasopressins

The relative roles of cardiopulmonary and sinoaortic baroreceptors in the regulation of vasopressin and corticosteroid release were evaluated in conscious dogs. The dogs were prepared with inflatable cuffs around either the ascending aorta, proximal to the brachiocephalic trunk, or the pulmonary artery. Inflation of the cuffs was adjusted to cause a reduction of mean systemic arterial pressure (MAP) of 0, 5, 10, 20, or 30% of control for 1 h in separate experiments. In spite of the profound systemic hypotension caused by constriction of the ascending aorta, plasma vasopressin failed to increase and corticosteroids increased only in response to a 30% decrease in MAP. In contrast, a 5% reduction in MAP during pulmonary arterial constriction increased plasma vasopressin and corticosteroid concentrations significantly. The apparent paradox in these results is correlated with different effects of the two maneuvers on left atrial pressure. Left atrial pressure increased dose dependently during inflation of the ascending aortic cuff but decreased during inflation of the pulmonary arterial cuff. In contrast, graded inflation of the pulmonary arterial cuff caused dose-dependent increases in right atrial pressure, plasma vasopressin, and corticosteroids. Therefore, we conclude that powerful inhibitory signals, arising from the left heart, can inhibit vasopressin and hypotension release in response to systemic hypotension.

Topics: Adrenal Cortex Hormones; Animals; Aorta; Constriction, Pathologic; Dogs; Female; Heart Conduction System; Hypotension; Male; Pressoreceptors; Pulmonary Artery; Vasopressins

Adrenocorticotropin (ACTH), cortisol, and vasopressin responses to clamped decreases in blood pressure (MAP) and to ovine corticotropin-releasing factor (CRF) infusion (20 ng X kg-1 X min-1) in intact and neurohypophysectomized (NHX) conscious dogs were examined. Mean arterial blood pressure was decreased 28 mmHg by a controlled infusion of sodium nitroprusside. Hypotension induced large increases in ACTH (peak 164 +/- 25 pg/ml), cortisol (peak 12.5 +/- 2.5 micrograms/dl), and vasopressin (peak 221 +/- 64 pg/ml) in intact (n = 7) dogs. NHX (n = 7) significantly attenuated these responses to hypotension. CRF infusion induced increases in ACTH similar in intact (n = 4) and NHX (n = 4) dogs. However, cortisol responses were significantly attenuated by NHX. Interestingly, CRF infusion induced small but significant increases in vasopressin from 3.0 +/- 1.1 to 8.1 +/- 2.0 pg/ml. We conclude that NHX attenuates ACTH and vasopressin responses to hypotension and cortisol responses to CRF-induced increases in ACTH. CRF seems to stimulate vasopressin release.

Topics: Adrenocorticotropic Hormone; Animals; Blood Pressure; Corticotropin-Releasing Hormone; Dogs; Heart Rate; Hydrocortisone; Hypophysectomy; Hypotension; Male; Nitroprusside; Pituitary Gland, Posterior; Vasopressins

Topics: Animals; Diprenorphine; Hematocrit; Hypotension; Male; Morphinans; Naloxone; Nitroprusside; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Shock; Vasopressins

A 50-year-old man underwent emergency aortic valve replacement. He had been treated with five antihypertensive agents before the procedure; this contributed to the development of profound hypotension after induction of anaesthesia. The hypotension did not respond to conventional treatment with an incremental intravenous infusion of phenylephrine HCl, probably due to the direct vasodilator action of the hydralazine group of drugs which renders the peripheral vascular smooth muscle unresponsive to sympathomimetic stimulation. The hypotension did, however, respond rapidly to low-dose infusion of a synthetic vasopressor, ornipressin (POR 8; Sandoz), a drug with a direct action on vascular smooth muscle, especially the capacitance vessels. Ornipressin thus restores vascular smooth-muscle tone even when the integrity of the adrenergic pathways is no longer intact.

Topics: Anesthesia, General; Antihypertensive Agents; Aortic Valve; Blood Pressure; Cardiopulmonary Bypass; Drug Resistance; Heart Valve Prosthesis; Humans; Hypotension; Intraoperative Complications; Male; Middle Aged; Muscle, Smooth, Vascular; Ornipressin; Phenylephrine; Vasopressins

In eight experiments in which a paired crossover design was used, we studied the ability of physiologic levels of cortisol to block adrenocorticotropic hormone (ACTH) and vasopressin responses to hypotension in fetal lambs. On different days, each fetus received a 4-hour infusion of cortisol or ethanol-saline solution vehicle, and then hypotension was induced with nitroprusside. Mean levels of ACTH before manipulation were 20 +/- 10 pg/ml and 18 +/- pg/ml in the saline solution- and cortisol-treated animals, respectively. Mean values of ACTH increased significantly to 70, 88, and 127 pg/ml at 2.5, 5, and 10 minutes of hypotension after pretreatment with saline solution. Cortisol pretreatment abolished the fetal ACTH response to hypotension. Mean levels of vasopressin during the control period were similar in the two groups of animals (5.7 +/- 1.5 pg/ml versus 5.9 +/- 1.3 pg/ml) and rose to comparable levels (69.4 +/- 15.6 pg/ml versus 65.2 +/- 7.7 pg/ml) during hypotension. Thus, increases in plasma cortisol levels within a physiologic range can suppress hypotension-induced ACTH but not vasopressin release in the fetus.

Topics: Adrenocorticotropic Hormone; Animals; Female; Fetal Diseases; Hydrocortisone; Hypotension; Pregnancy; Radioimmunoassay; Sheep; Vasopressins

Rats were treated with a single injection of either capsaicin (50 mg kg-1 s.c.) or vehicle on day 2 after birth. When the animals were adult, they were challenged with osmotic (water deprivation) and haemodynamic (acute hypotension) stimuli that normally evoke vasopressin release. Capsaicin-treated and vehicle-injected rats showed similar body weight losses and plasma osmolalities following 48 h of water deprivation. Thus it appears that neonatal treatment with capsaicin does not impair the antidiuretic response to plasma hyperosmolality. Following acute ganglion blockade in the presence of angiotensin converting enzyme inhibition, there was some recovery of blood pressure in the vehicle-injected rats, but recovery was significantly (P less than 0.001) less in the capsaicin-treated animals. The recovery may be attributed to vasopressin since it was abolished by an antagonist selective for the pressor action of the peptide (d(CH2)5DAVP). These results suggest that neonatal treatment with capsaicin impairs vasopressin-mediated recovery of blood pressure following acute hypotension. The possible involvement of baro- or chemoreceptor afferents is discussed.

Topics: Acute Disease; Animals; Animals, Newborn; Blood Pressure; Capsaicin; Female; Hypotension; Male; Rats; Rats, Inbred Strains; Vasopressins; Water Deprivation

We demonstrated previously that cerebellectomy or ablation of the fastigial nuclei (FN) in the dog impairs markedly the restoration of blood pressure and increases the death rate after severe hypotension. Angiotensin (AII) and vasopressin (AVP) participate in the pressor response to hypotension, and plasma levels of both are increased by electrical stimulation of the FN. The present studies examined the importance of the FN in mediating the secretion of AII and AVP after hemorrhage to 50 mm Hg. Cerebellectomy reduced significantly both the rate of recovery and level of maintenance of blood pressure after hemorrhage. Blockade of conversion of AI of AII with captopril produced a similar deficit, and combination of both treatments produced a greater impairment than either alone. Treatment with an AVP antagonist decreased the level of maintenance of blood pressure but not be initial rate of recovery. The AVP antagonist in combination with cerebellectomy did not produce a greater deficit than cerebellectomy alone. This would suggest that although the cerebellum mediates some activation of the renin-angiotensin system during severe hypotension, it may mediate most of the AVP secretion under these conditions.

Topics: Angiotensin II; Animals; Blood Pressure; Cerebellum; Dogs; Female; Hemorrhage; Hypotension; Male; Vasopressins

Substance P (SP) and analogs, including 5 nucleoside (ARA or HRA)-peptides, were examined for antidiuretic activity in ethanolized rats. The activity was potent in the analogs embodying the C-terminal hexapeptide, weak in the nucleoside-pentapeptide, and negligible in the nucleoside-tetrapeptide. In addition, the activity was increased by acylation of the hexapeptide. The antidiuretic potencies were also compared with the hypotensive potencies.

Topics: Animals; Blood Pressure; Diuresis; Hypotension; Male; Rats; Structure-Activity Relationship; Substance P; Vasopressins

Topics: Angiotensin II; Animals; Body Water; Dogs; Fluid Therapy; Hypotension; Isotonic Solutions; Osmotic Pressure; Ringer's Lactate; Shock, Hemorrhagic; Vasopressins

A syndrome of chronic hypernatremia (range 148 to 161 mmoles/l) and partial hypopituitarism (growth hormone and gonadotropin deficiencies) is reported in a 27 year-old man with sarcoid hypothalamic involvement. The patient did not complain of thirst and spontaneous fluid intake was not sufficient to restore the serum sodium to normal. However, when larger amounts of water were given (50 ml/kg for 180 min), the plasma osmolality returned to normal values in 3 hours. Blood volume values were found subnormal on two occasions on free diet (63 and 74% of the theorical normal values) and plasma renin activity was elevated (22 ng/ml/hour). Plasma vasopressin (AVP) concentrations (range < 1 to 1.9 pg/ml) were inappropriately low for the degree of plasma osmolality and remained markedly subnormal when hypertonic saline was infused (NaCl 5%, 10 ml/min for 60 min). However, the secretory stores and hemodynamic control of AVP release were intact since a rise in plasma AVP to 10.8 pg/ml was observed after induction of arterial hypotension with sodium nitroprusside infusion. These results provide further direct evidence fo the dysfunction of the thirst mechanism and the osmotic contol of AVP release. They support the concept that osmoreceptor areas are anatomically distinct from the neurohypophyseal AVP secretory system and that neural inputs from baroreceptor and osmoreceptor cells are completely separated.

Topics: Adult; Blood Volume; Fluid Therapy; Humans; Hypernatremia; Hypopituitarism; Hypotension; Hypothalamus; Male; Nitroprusside; Osmolar Concentration; Renin; Sarcoidosis; Thirst; Vasopressins; Water-Electrolyte Balance

Using unanaesthetized monkeys, experiments were performed to examine the effects of haemorrhage on the liberation of arginine vasopressin (AVP). Haemorrhages of 10%, 15% or 20% total blood volume were performed via a catheter with its tip in the abdominal vena cava. A catheter in the left internal jugular vein was used for blood sampling. Arterial blood pressure was monitored via a catheter whose tip resected in an iliac artery. The monkeys showed no signs of discomfort from this catheterisation. Blood samples for AVP assay were taken at different times from 0-90 min after the end of the haemorrhage. At the end of the experiment, blood removed was reinfused. Results show that haemorrhage resulted in liberation of AVP, but only if there was a fall in arterial blood pressure. AVP release occurred more readily as the total volume of blood withdrawn increased, but the absolute rise in hormone concentration was not related to the total volume of blood withdrawn. However, comparing the area under the curve of mean arterial blood pressure with that for AVP concentration showed the two to have a significant exponential relationship. It is concluded that, as in other species, haemorrhage is a potent stimulus for AVP liberation in the monkey. However, in contrast to some other species, the fall in arterial pressure seems to be the prime stimulus rather than hypovolemia per se.

Topics: Animals; Arginine Vasopressin; Blood Volume; Haplorhini; Heart Rate; Hemorrhage; Hypotension; Macaca mulatta; Male; Respiration; Vasopressins

Mild vasovagal hypotension occurred in two normal male volunteers during insertion of indwelling venous cannulae. In spite of a rapid intravenous fluid load (3.6-4.6 litres in 90 min) both subjects passed little urine for 100 min. When the experiment was repeated without vasovagal hypotension, a rapid large diuresis followed the fluid load. The prolonged oliguria after vasovagal hypotension was the result of vasopressin release. This was demonstrated by measuring vasopressin in the blood and urine and by observing the renal response to a water load. The observation in man that a mild transient hypotensive episode may reduce urine flow for 100 min has clinical significance.

Topics: Catheterization; Diuresis; Humans; Hypotension; Male; Vagus Nerve; 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

Topics: Angiotensin II; Animals; Blood Vessels; Catecholamines; Drug Interactions; Heart Rate; Homeostasis; Humans; Hypotension; Kidney; Kidney Cortex; Lipid Metabolism; Molecular Conformation; Prostaglandins; Renin; Sodium; Vascular Resistance; Vasopressins; Water-Electrolyte Balance

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

Topics: Animals; Blood Pressure; Female; Hemorrhage; Hypotension; Male; Phenoxybenzamine; Phentolamine; Pituitary Gland, Posterior; Rats; Vasopressins

Topics: Animals; Antibodies, Viral; Apnea; Autopsy; Blood; Brain; Carbon Dioxide; Child; Chlorpromazine; Diabetes Insipidus; Fluorescent Antibody Technique; Heart Arrest; Humans; Hydrogen-Ion Concentration; Hyperkinesis; Hypotension; Male; Mice; Oxygen; Rabies; Rabies virus; Seizures; Vasopressins

Topics: Autopsy; Blood Glucose; Blood Urea Nitrogen; Brain Diseases; Caudate Nucleus; Cerebral Cortex; Corpus Callosum; Creatinine; Demyelinating Diseases; Diabetic Coma; Female; Humans; Hypotension; Male; Metabolic Diseases; Middle Aged; Osmolar Concentration; Pons; Sodium; Vasopressins; Water-Electrolyte Balance

Topics: Angiotensin II; Animals; Capillaries; Felypressin; Hypotension; Male; Microcirculation; Muscles; Norepinephrine; Rats; Regional Blood Flow; Shock, Hemorrhagic; Vasopressins

Topics: Angiotensin II; Animals; Blood Pressure; Blood Volume; Dogs; Hemorrhage; Hypotension; Lymph; Metaraminol; Microcirculation; Norepinephrine; Ornithine; Oxygen; Partial Pressure; Phenylephrine; Vasoconstrictor Agents; Vasopressins

The effect of octapressin (2-phenylalanine-8-lysine vasopressin) on renal and intrarenal blood flow was studied in 11 normotensive cirrhotic patients with abnormal renal perfusion. Renal haemodynamic changes were assessed with the (133)Xenon washout technique. Of the six patients given suppressor doses of octapressin intravenously renal blood flow improved in one only. A further three patients responded to the drug in a dose which increased the mean arterial pressure by 5 or more mm Hg. The increase in mean renal blood flow was accompanied by an improvement in renal cortical perfusion. In two patients renal blood flow decreased after the administration of octapressin. These findings, in conjunction with previous reports, suggest that octapressin will only consistently improve renal perfusion in cirrhotic subjects who are hypotensive and in whom the mean arterial blood pressure is raised by the drug, but do not exclude the possibility that octapressin may have a direct renal circulatory effect in some patients.

Topics: Adult; Alkaline Phosphatase; Bilirubin; Blood Flow Velocity; Blood Pressure; Creatinine; Felypressin; Female; Humans; Hypertension, Portal; Hypotension; Kidney; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Serum Albumin; Vasopressins; Xenon

1. Study of the delayed responses to lethal doses of endotoxin in cats is complicated by acute pulmonary vasoconstriction which results in hypotension, cardiac failure and pulmonary oedema. This acute response is abolished if the animal is pretreated with aspirin (10-100 mg/kg). In these cats, pretreated with aspirin, arterial pressure and right atrial pressure remain unchanged in the first 2 h after administration of endotoxin. Later, arterial pressure falls and the animals die but no haemorrhagic lung lesions are visible.2. These results confirm our previous conclusion that the delayed lethal response to endotoxin is an independent action and not a secondary consequence of the acute response. The mechanism of the action of aspirin is discussed and it is suggested that it prevents the release by endotoxin of vasoactive substances, possibly from platelets.3. In cats pretreated with aspirin, administration of endotoxin results in a marked mesenteric vasoconstriction. Although arterial pressure does not decrease significantly, superior mesenteric arterial flow decreases to 20% of control in the first hour after endotoxin and remains at this low level until the animal dies. Mesenteric ischaemia may contribute to the cat's death.4. The mesenteric vasoconstriction is not reduced by prior administration of phenoxybenzamine and is only slightly reduced after phenoxybenzamine, hypophysectomy and nephrectomy. It is concluded that catecholamines, vasopressin and angiotensin play at most a minor role in the mechanism of this vasoconstriction and that other unknown factors are predominant.

Topics: Angiotensin II; Animals; Aspirin; Blood Platelets; Blood Pressure; Cats; Endotoxins; Heart Failure; Hypophysectomy; Hypotension; Ischemia; Mesenteric Arteries; Nephrectomy; Phenoxybenzamine; Pulmonary Edema; Time Factors; Vasoconstrictor Agents; Vasopressins

Topics: Animals; Dogs; Female; Ferricyanides; Hemorrhage; Hypotension; Male; Vasopressins

Topics: Animals; Blood Pressure; Carbamates; Female; Ganglionic Stimulants; Guanethidine; Hypertension, Renal; Hypotension; Nicotine; Norepinephrine; Physostigmine; Piperazines; Pyrrolidines; Quaternary Ammonium Compounds; Rats; Tachyphylaxis; Tyramine; Vasopressins

1. Water-loaded rats under ethanol anaesthesia were used to determine whether bradykinin releases ADH and whether the release is a reflex response to hypotension or the result of direct stimulation of the central nervous system by the peptide.2. Intravenous injections of bradykinin caused hypotension followed by prolonged antidiuresis; both responses were dose dependent.3. The antidiuresis caused by bradykinin could not be accounted for by hypotension alone. Haemorrhage and intravenous injections of isoprenaline, which caused falls in arterial blood pressure similar to those caused by bradykinin, produced only short-lasting antidiuretic responses.4. Intracarotid injections of bradykinin caused antidiuresis with little or no preceding hypotension. No antidiuresis was produced by intracarotid injections of isoprenaline.5. After intravenous injection of bradykinin, small amounts of ADH were identified in whole blood and, on a few occasions only, in concentrated urine. However, ADH was not detected in blood extracts.6. After intravenous injection of nicotine in doses which caused antidiureses similar to that caused by bradykinin, ADH was regularly detected in large amounts in blood extracts and in unconcentrated urine.7. Bradykinin did not cause prolonged antidiureses when injected into a rat with congenital diabetes insipidus.8. ADH release was not increased when isolated rat neural lobes were incubated with bradykinin although release was elevated by an increase in the K(+) concentration of the incubation medium.9. It is suggested that bradykinin causes release of an antidiuretic substance by a direct action on the central nervous system. The possibility that this substance is ADH is discussed.

Topics: Animals; Blood Pressure; Bradykinin; Carotid Arteries; Central Nervous System; Diabetes Insipidus; Diuresis; Female; Hemorrhage; Hypotension; Injections, Intra-Arterial; Injections, Intravenous; Isoproterenol; Male; Nicotine; Pituitary Gland, Posterior; Potassium; Rats; Vasopressins

Topics: Animals; Blood Pressure; Bloodletting; Dextrans; Dogs; Female; Hypotension; Kidney; Kidney Concentrating Ability; Kidney Tubules; Perfusion; Vasopressins

Topics: Acute Kidney Injury; Anesthesia; Blood Pressure; Glomerular Filtration Rate; Hemorrhage; Hepatic Artery; Humans; Hypotension; Kidney; Liver Circulation; Sympathetic Nervous System; Urine; Vascular Resistance; Vasopressins

Topics: Adult; Cardiac Surgical Procedures; Female; Heart Septal Defects; Humans; Hypotension; Hypothalamus; Mitral Valve Stenosis; Polyuria; Postoperative Complications; Vasopressins

Topics: Child; Coma; Epilepsy, Tonic-Clonic; Humans; Hyponatremia; Hypotension; Leukemia, Lymphoid; Male; Reflex, Abnormal; Vasopressins; Vincristine

Topics: Adolescent; Adult; Aged; Blood Pressure; Child; Child, Preschool; Felypressin; Female; Humans; Hypotension; Male; Middle Aged; Postoperative Complications; Vasopressins

Topics: Adrenal Cortex Hormones; Adult; Catecholamines; Endocrine System Diseases; Humans; Hypotension; Middle Aged; Parathyroid Hormone; Thyroxine; Vasopressins

Topics: Animals; Barium; Calcium; Dogs; Hemorrhage; Hypotension; Hypothalamo-Hypophyseal System; In Vitro Techniques; Male; Microscopy, Electron; Neurosecretion; Pituitary Gland, Posterior; Potassium; Vasopressins

Topics: Adult; Aged; Anesthesia; Animals; Blood Pressure; Felypressin; Female; Humans; Hypotension; Male; Mice; Middle Aged; Vasopressins

Topics: Anesthesia, Spinal; Angiotensin II; Blood Pressure; Glucocorticoids; Humans; Hypotension; Sympathomimetics; Vasopressins

Topics: Adenosine Triphosphate; Animals; Blood; Blood Pressure; Bradycardia; Carotid Arteries; Hypotension; Pyrophosphatases; Rats; Sympatholytics; Vasopressins; Water

Topics: Animals; Constriction; Creatine; Creatinine; Diuresis; Dogs; Hypotension; Kidney Function Tests; Kidney Glomerulus; Osmosis; Pathology; Renal Artery Obstruction; Research; Shock, Hemorrhagic; Vasopressins

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Dogs; Hemorrhage; Hypotension; Kidney; Rubidium; Thyroid Gland; Vasopressins

Topics: Angiotensins; Blood Pressure Determination; Central Nervous System Stimulants; Heart Arrest; Heart Failure; Humans; Hypotension; Pharmacology; Postoperative Care; Postoperative Complications; Shock; Sympathomimetics; Toxicology; Vascular Diseases; Vasopressins; Water-Electrolyte Balance

Topics: Addison Disease; Arginine Vasopressin; Avena; Bronchial Neoplasms; Carcinoma, Small Cell; Cushing Syndrome; Gynecomastia; Humans; Hypercalcemia; Hyperthyroidism; Hyponatremia; Hypotension; Liver Cirrhosis; Male; Metabolism; Pathology; Physiology; Small Cell Lung Carcinoma; Sodium; Vasopressins

Topics: Emergencies; Heart Arrest; Heart Massage; Histamine H1 Antagonists; Humans; Hypotension; Infusions, Parenteral; Podiatry; Seizures; Spasm; Tachycardia; Vasopressins; Vocal Cord Paralysis

Topics: Cortisone; Desoxycorticosterone; Diagnosis; Ephedrine; Extrapyramidal Tracts; Fludrocortisone; Humans; Hypotension; Hypotension, Orthostatic; Neurologic Manifestations; Phenylephrine; Physical Therapy Modalities; Posture; Pure Autonomic Failure; Vasopressins