Exogenous Vasopressin Research Articles

The cardioprotective effect of different doses of vasopressin (AVP) against ischemia–reperfusion injuries in the anesthetized rat heart

The aim of the present study was to investigate the protective effect of various doses of exogenous vasopressin (AVP) against ischemia–reperfusion injury in anesthetized rat heart. Anesthetized rats were randomly divided into seven groups ( n = 4–13) and all of them subjected to prolonged 30 min regional ischemia and 120 min reperfusion. Group I served as saline control with ischemia, in treatment groups II, III, IV and V, respectively different doses of AVP (0.015, 0.03, 0.06 and 1.2 μg/rat) were infused within 10 min prior to ischemia, in group VI, an AVP-selective V1 receptor antagonist (SR49059, 1 mg/kg, i.v.) was administrated prior to effective dose of AVP injection and in group VII, SR49059 (1 mg/kg, i.v.) was only administrated prior to ischemia. Various doses of AVP significantly prevented the decrease in heart rate (HR) at the end of reperfusion compared to their baseline and decreased infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB) and MDA (malondialdehyde) plasma levels], severity and incidence of ventricular arrhythmia, episodes and duration of ventricular tachycardia (VT) as compared to control group. Blockade of V1 receptors by SR49059 attenuated the cardioprotective effect of AVP on ventricular arrhythmias and biochemical parameters, but partially returned infarct size to control. AVP 0.03 μg/rat was known as effective dose. Our results showed that AVP owns a cardioprotective effect probably via V1 receptors on cardiac myocyte against ischemia/reperfusion injury in rat heart in vivo.

Detectability of Vasopressin in Continuous Venovenous Hemodialysis Effluent of Patients with Vasodilatory Shock Treated with Exogenous Arginine Vasopressin

To determine whether vasopressin is detectable in the continuous venovenous hemodialysis (CVVHD) effluent of patients receiving exogenous arginine vasopressin, and to determine whether treatment-specific factors are associated with vasopressin levels in CVVHD effluent. DESIGN. Prospective observational study. SETTING. Intensive care units of a tertiary care academic medical center. PATIENTS. Twenty-seven adults with vasodilatory shock who received a stable-dose continuous intravenous infusion of arginine vasopressin with concomitant uninterrupted CVVHD for at least 4 hours between September 2008 and May 2010. MEASUREMENTS AND MAIN RESULTS. Vasopressin levels in CVVHD effluent were assessed by radioimmunoassay. Statistical analysis was performed with analysis of variance and Pearson correlation. A multivariate linear regression was used to assess for independent factors associated with vasopressin levels in CVVHD effluent. The CVVHD effluent of all patients was assessed for vasopressin levels. The median exogenous arginine vasopressin dose was 0.03 unit/minute (range 0.02-0.18 unit/min), whereas the median CVVHD effluent flow rate was 22.6 ml/kg/hour (interquartile range [IQR] 21.5-26.8 ml/kg/hr). Vasopressin was detectable in all effluent samples (median 88.8 pg/ml, IQR 36.4-113.7 pg/ml). There were no significant differences in CVVHD effluent vasopressin levels among CVVHD filter types (p=0.39). The CVVHD effluent vasopressin levels correlated with exogenous arginine vasopressin dose (r2=0.49, p<0.001). After adjustment for CVVHD effluent flow rate and administration of corticosteroids, with multivariate linear regression, only exogenous arginine vasopressin dose was independently associated with CVVHD effluent vasopressin level. CONCLUSION. Vasopressin is detectable in CVVHD effluent, suggesting that it is removed by CVVHD. In addition, exogenous arginine vasopressin infusion dose is independently associated with CVVHD effluent vasopressin level.

Vasopressin Deficiency and Vasodilatory State in End-Stage Liver Disease

Relative vasopressin deficiency, a contributor to vasodilatory septic shock, also may be a cause of the vasodilatory state in liver disease. This study assessed endogenous vasopressin levels in patients with liver disease and their hemodynamic response to exogenous vasopressin. A prospective, observational study. A single-center, tertiary hospital. Human subjects undergoing liver transplantation or major surgery. Vasopressin levels were measured in 28 patients with liver disease undergoing liver transplantation and 7 control patients with normal liver function. Additionally, intravenous vasopressin was administered to 20 liver transplant recipients, and the hemodynamic response was observed. Patients with liver disease had significantly lower baseline vasopressin levels than controls (19.3 ± 27.1 pg/mL v 50.9 ± 36.7 pg/mL, p = 0.015). Patients with low vasopressin levels (≤20 pg/mL) were more likely to have lower baseline mean blood pressure (≤80 mmHg) than patients with high vasopressin levels (11/16 v 0/4, p = 0.013). Systemic vascular resistance increased by 33% 3 minutes after intravenous vasopressin. Thirteen of 16 patients with low vasopressin levels compared with 1 of 4 patients with high vasopressin levels responded to exogenous vasopressin, with an increase of mean blood pressure by more than 20% (p = 0.028). Patients with liver disease have lower vasopressin levels than controls and respond with a brisk vasoconstrictor response to exogenous vasopressin. Therefore, relative endogenous vasopressin deficiency may contribute to vasodilatory shock in liver disease similar to what has been observed in septic shock.

Arginine vasopressin plasma levels could indicate childern undergoing cardiopulmonary bypass that might benefit from exogenous arginine vasopressin*

Arginine vasopressin plasma levels could indicate childern undergoing cardiopulmonary bypass that might benefit from exogenous arginine vasopressin*

The effectiveness of vasopressin as an ACTH secretagogue in cattle differs with temperament

By using the temperament selection criterion of exit velocity (EV), cattle typically exhibiting hypercortisolism and a blunted response to exogenous corticotrophin-releasing hormone (CRH) can be identified via individual behavioral responses to handling. To further characterize hypothalamic–pituitary–adrenal (HPA) axis dysfunction associated with bovine temperament, the present study compared pituitary and adrenal activity, following stimulation with exogenous vasopressin (VP), in steers with an excitable or calm temperament. Serial blood samples were collected via indwelling jugular cannula for 6 h preceding and 6 h following administration of a VP bolus. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were quantified by RIA to determine pituitary and adrenal responsiveness within temperament groups. Cortisol concentrations in excitable steers during the pre-challenge period revealed an increased initial adrenal reactivity to interactions with humans. Subsequent acclimation to the experimental surroundings yielded greater baseline cortisol concentrations in the cattle with an excitable temperament. Pituitary stimulation with VP resulted in a greater ACTH output from the excitable compared to the calm animals. The data presented herein provide additional evidence that HPA axis function in cattle of an excitable temperament may be akin to a state of chronic stress. The bovine temperament model may be of further use to both decipher mechanisms associated with HPA dysfunction and to elucidate physiological phenotypes or pathologies that have parallels in other species.

Reduced Walker 256 carcinosarcoma growth in vasopressin-deficient Brattleboro rats

The growth pattern of carcinosarcoma Walker 256 was studied in rats with different levels of vasopressin in the blood. The Brattleboro rats are unable to synthesize vasopressin in a consequence of deletion in the coding gene. Hybrids from crossbreeding of the mutant Brattleboro and normal WAG rats inherit the one intact vasopressin gene and hold nearly normal hormone level. It was found that non-strain-specific carcinosarcoma Walker 256 intensively grows in WAG rats and their offsprings from crossbreeding with Brattleboro rats, and tumor development is equally terminated in them by death. Carcinosarcoma grows less intensely in Brattleboro rats; the tumor nodes increased only within the first 2weeks, after which, the tumor began to decrease and eventually disappeared. Infusion of exogenous vasopressin to Brattleboro rats intensifies a tumor growth in the first 2weeks after the inoculation of Walker 256 cells; however, it does not prevent a following regression and resorption of tumors.

Extracorporeal Membrane Oxygenation (ECMO) Does Not Restore Renal Autoregulation in Endotoxin‐Induced Acute Renal Failure

Endotoxin‐induced shock may be treated with ECMO for cardiopulmonary support. Renal function during ECMO may be altered due to partial cardiopulmonary bypass and altered regulation of cardiovascular regulating hormones. In anesthetized pigs (n=8), we compared renal function at baseline, after endotoxic shock with acute renal failure was established (via i.v. injection of E coli endotoxin), and after 2 hours of stabilization on venoarterial ECMO. Endotoxin caused a mean arterial pressure (MAP) 33% decrease (p≤0.05) from 88±3 to 59±3 mm Hg. ECMO could maintain blood flow to prevent any further deterioration of MAP, but did not return MAP (56±4 mm Hg) to baseline. Interestingly, the 59% decrease (p≤0.05) in renal microcirculatory blood flow (as measured by microsphere method) caused by endotoxin, was prevented from dropping further with ECMO. However, the endotoxin‐induced 76% decrease in GFR (p≤0.05) continued to decline with ECMO resulting in deterioration of urine flow towards complete renal shut down. The urine flow decrease was due mainly to a decrease in osmotic clearance. Results are consistent with the drop of endogenous vasopressin (VP) levels seen with ECMO that we previously reported. We and others have demonstrated that exogenous VP at high doses is needed to reverse renal shut down. Results suggest that during ECMO, VP replacement therapy may be necessary to restore renal perfusion pressure to maintain urine flow.

Vasopressin in Hemorrhagic Shock: Review Article

Trauma with resultant hypovolemic shock remains both prevalent and difficult to treat. Standard strategies using volume resuscitation and catecholamine support have historically yielded poor results. Vasopressin has emerged as a possible pharmacologic adjunct, particularly in patients with shock refractory to the administration of fluids and catecholamines. Much of the data regarding vasopressin is extrapolated from its usefulness in cases of nonhypovolemic human shock, which are supported by convincing animal studies. It is true that humans show a deficiency in vasopressin minutes after significant hemorrhage that can respond to administration of exogenous vasopressin. When given in physiological dosing regimens, vasopressin appears to be a safe adjunct to other therapy. Definite recommendations regarding indications for use, recommended dose, and long-term outcome in patients with hemorrhagic shock await a much needed prospective, randomized, controlled trial.

Endogenous and Exogenous Vasopressin during Hemodialysis

Intradialytic hypotension likely results from hypovolemia as well as patient and dialysis-specific factors. An impaired vasoconstrictive response to volume loss during hemodialysis has been demonstrated and increasing evidence suggests that deficiency in the hormone arginine vasopressin may be a contributing factor. Although vasopressin is widely recognized for its role in the regulation of serum osmolality, vasopressin is also an important regulator of blood pressure in health and in various disease states. That vasopressin deficiency contributes to the pathogenesis of intradialytic hypotension is suggested by several observations. First, vasopressin levels typically fall during hemodialysis when a rise might be expected as a result of volume loss. Second, therapies that prevent a fall in osmolality during dialysis, including dialysis against a high sodium bath and isolated ultrafiltration, have been shown to improve intradialytic blood pressure stability. Finally, and perhaps most importantly, the administration of low-dose exogenous vasopressin during dialysis has been shown to support blood pressure and improve volume removal. Further research is needed to determine the effect of chronic vasopressin (or selective V1a agonist) administration during dialysis on volume removal, inter- and intradialytic blood pressure control, and, ultimately, clinical outcomes in end-stage renal disease patients on dialysis.

Interactions between angiotensin II and arginine vasopressin in water homeostasis

Mice deficient in the angiotensin II type 1a (AT(1a)) receptor demonstrate a vasopressin-resistant nephrogenic diabetes insipidus. These knockout mice exhibit a threefold increase in 24-h urine excretion. Neither 2 weeks of exogenous vasopressin nor 5 days of fluid restriction reversed this polyuric state. This nephrogenic diabetes insipidus was associated with reductions in adenylyl cyclase protein and in the phosphorylated mitogen-activated protein kinase extracellular signal-regulated kinase 1/2. The results support an important interaction between vasopressin and angiotensin II in maximal urinary concentration.

Vasopressin Does Not Mediate Hypersensitivity of the Hypothalamic Pituitary Adrenal Axis during Chronic Stress

The hypothesis that vasopressin (VP) becomes the main mediator of pituitary corticotroph responsiveness during chronic hypothalamic pituitary adrenal (HPA) axis activation was tested by examining the effect of pharmacologic VP receptor blockade on the adrenocorticotropic hormone (ACTH) and corticosterone responses of 14-day repeatedly restrained rats. In spite of the increased vasopressinergic activity, repeatedly restrained rats showed lower ACTH and corticosterone responses to 10 min white noise compared with handled controls. These responses were unchanged by injection of the nonpeptide-selective V1b receptor antagonist SSR149415 i.v., 1 h before noise application. In contrast to noise stress, plasma ACTH responses to i.p. hypertonic saline injection were enhanced in the repeatedly restrained rats compared with handled controls, but responses were also unaffected by SSR149415 administered orally, daily 1 h before restraint. Since SSR149415 effectiveness was low, we used minipump infusion of the peptide V1 receptor antagonist, dGly[Phaa1,D-tyr(et), Lys, Arg]VP (V1-Ant) for 14 days, which effectively blocked ACTH responses to exogenous VP. Chronic V1-Ant infusion reduced plasma ACTH responses to i.p. hypertonic saline in handled controls but not in repeatedly restrained rats. These data suggest that the increased vasopressinergic activity characteristic of chronic stress plays roles other than mediating the hypersensitivity of the HPA axis to a novel stress.

Vascular Effects of RWJ-676070, a Selective Combined V1a/V2 Vasopressin Receptor Antagonist

In recent years, several vasopressin antagonists have been developed that block V1 receptors either selectively or nonselectively.1,2 To date, one combined V1/V2 antagonist (primarily a V2 antagonist, as determined on the basis of human receptor binding data), conivaptan, has been approved for the treatment of euvolemic hyponatremia.3,4 We have previously shown that the vascular properties of a vasopressin V1 antagonist can be investigated safely and reliably in healthy subjects. We used the measurement of skin blood flow after intradermic injection of exogenous arginine vasopressin on a skin area prevasodilated with calcitonin gene–related peptide (CGRP).3,5 This technique enables the documentation of the dose-dependent effects of vasopressin or vasopressin antagonists. In this study, we have characterized the V1a pharmacodynamic profile of increasing doses of RWJ-676070, a new orally active dual V1a/V2 receptor antagonist, in healthy subjects.5 Clinical Pharmacology & Therapeutics (2009); 85, 2, 145–148 doi:10.1038/clpt.2008.217

Regulation of Coronary Blood Flow During Exercise

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac outpu...

Effects of Vasopressin in Septic Shock

Septic shock continues to be one of the leading causes of death in the intensive care unit today. The confluence of many factors contributes to the deterioration of patients’ condition in septic shock. Increased levels of nitric oxide, in part, mediate the cardiovascular effects of septic shock. Nitric oxide is major mediator of vasodilation and hypotension as well as myocardial depression. It also contributes to decreased production and release of endogenous vasopressin. Vasopressin effects are actualized by stimulation of V1, V2, and V3 receptors located in various parts of the body. The response is dose dependent. Endogenous vasopressin and angiotensin II act synergistically to preserve and restore blood pressure levels. Decreased circulating vasopressin contributes to adrenal insufficiency via hypothalamic-pituitary-adrenal axis suppression and increased catecholamine resistance to vasopressors. Exogenous vasopressin supplementation in physiologic doses has been shown to improve blood pressure levels and decrease vasopressor needs in patients with septic shock.

Effects of Vasopressin in Septic Shock

Septic shock continues to be one of the leading causes of death in the intensive care unit today. The confluence of many factors contributes to the deterioration of patients' condition in septic shock. Increased levels of nitric oxide, in part, mediate the cardiovascular effects of septic shock. Nitric oxide is major mediator of vasodilation and hypotension as well as myocardial depression. It also contributes to decreased production and release of endogenous vasopressin. Vasopressin effects are actualized by stimulation of V1, V2, and V3 receptors located in various parts of the body. The response is dose dependent. Endogenous vasopressin and angiotensin II act synergistically to preserve and restore blood pressure levels. Decreased circulating vasopressin contributes to adrenal insufficiency via hypothalamic-pituitary-adrenal axis suppression and increased catecholamine resistance to vasopressors. Exogenous vasopressin supplementation in physiologic doses has been shown to improve blood pressure levels and decrease vasopressor needs in patients with septic shock.

A differential response in the reproductive system and energy balance of spiny mice Acomys populations to vasopressin treatment

Increased dietary salinity suppressed reproduction of the xeric adapted golden spiny mouse, Acomys russatus. Testicular and uterine mass were reduced, suppressed spermatogenesis and vaginal closure were observed. The anti-diuretic hormone, vasopressin (VP), was suggested to mediate such effects. However, increased dietary salinity did not affect reproductive status of a mesic adapted population of the common spiny mouse, A. cahirinus. In the present study, the effect of exogenous VP on the reproductive status and energy balance of both males and females of A. russatus and of a mesic population of A. cahirinus was tested. Vasopressin (Sigma, 50 µg/kg) was injected intraperitoneally in three-day intervals for four weeks. In VP -treated A. russatus, spermatogenesis was significantly suppressed while the change in testis mass did not show significant difference. Both control and VP-treated females lost body mass ( W b) significantly and the latter also exhibited a higher energy expenditure compared to their male counterparts. VP did not affect reproductive status in both sexes of A. cahirinus. Also it did not have a significant effect on W b, energy intake, and energy expenditure in this species. Our results support the idea that VP mediates the effects of increased diet salinity on reproduction in A. russatus. The results also reinforce previous knowledge that different physiological systems could be integrated by a single biochemical signal.

Hemodynamic effects of association of vasopressin and norepinephrine in patients with septic shock

Patients in septic shock (SS) produce inappropriately low amounts of vasopressin [1]. The purpose of our study was to analyze hemodynamic effects of association of exogenous arginine vasopressin (VP) and low doses of norepinephrine (NE) in critically ill patients with septic shock.

Endogenous and exogenous vasopressin in shock

Vasopressin is critical for blood pressure regulation when cardiovascular homeostasis is threatened and some patients with shock have inappropriately low levels of hormone in plasma. The present review focuses on recent work that addresses the role of endogenous vasopressin in the pathogenesis of shock and the potential therapeutic indications and secondary effects of exogenous hormone in patients with shock. Examples of types of shock resistant to catecholamine pressors in which exogenous vasopressin was effective in restoring arterial pressure continued to accumulate. Widespread determinations of plasma vasopressin in patients with shock suggest that endogenous vasopressin deficiency may be more frequent than previously thought. The generation of mice with deletion of vasopressin's V1a receptor highlighted the important role of the hormone on cardiovascular homeostasis. Vasopressin administration is very effective in restoring arterial pressure in many forms of shock and this appears to be due, at least in part, to deficiency of endogenous hormone. Generation of mice lacking vasopressin V1a receptor open new and exciting avenues of inquiry to clarify the role of the hormone in cardiovascular homeostasis.

Profound vasodilatory hypotension in a patient with known empty sella syndrome following cardiac surgery

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.

Vasopressin Mediates Mitogenic Responses to Adrenalectomy in the Rat Anterior Pituitary

To determine whether increased vasopressinergic activity during chronic stress or adrenalectomy mediates trophic changes in the corticotroph, we examined the effect of peripheral V1 receptor blockade in rats, using the antagonist, dGly[Phaa1,D-tyr(et), Lys, Arg]vasopressin (VP), on the number of pituitary cells taking up bromodeoxyuridine (BrdU) and cells containing immunoreactive ACTH (irACTH). Adrenalectomy significantly increased the number of BrdU- and ACTH-labeled cells at 3 and 6 d, and a much larger increase was observed at 28 d. Minipump infusion of V1 antagonist for 28 d, at doses blocking the increases in ACTH and corticosterone induced by exogenous VP, prevented the increases in BrdU incorporation, but not irACTH cells observed 28 d after adrenalectomy. Unexpectedly, colocalization of BrdU with ACTH-positive cells was minor (about three cells per pituitary section), and this was unaffected by adrenalectomy or V1 antagonist infusion. In contrast, adrenalectomy for 6 or 14 d failed to increase BrdU incorporation or irACTH cells in V1b receptor knockout mice while inducing the expected increase in wild-type mice. The data show that VP is required for pituitary mitogenesis after adrenalectomy but, at least in rats, not for increasing the number of corticotrophs. The lack of colocalization of ACTH in mitotic cells suggests that recruitment of corticotrophs during adrenalectomy occurs from undifferentiated cells.