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PubMed1993

Mitogenic events induced by vasopressin in aortic fibroblasts from spontaneously hypertensive rats.

1. To further explore the mechanisms of arterial growth, we investigated the signalling pathways through which arginine-vasopressin acts as a mitogen in cultured adventitial aortic fibroblasts of the spontaneously hypertensive rat, and we examined the mechanisms involved in the hyperresponsiveness to arginine-vasopressin of fibroblasts from spontaneously hypertensive rats compared with fibroblasts from Wistar-Kyoto rats. 2. Arginine-vasopressin-induced [3H]thymidine incorporation was used to determine the peptide mitogenicity. Arginine-vasopressin-triggered hydrolysis of phosphoinositides by phospholipase C was evaluated by measuring [3H]inositol phosphate formation. The role of protein kinase C and protein tyrosine kinases in arginine-vasopressin mitogenicity was assessed by stimulating the cells with arginine-vasopressin in the presence of 12-O-tetradecanoylphorbol 13-acetate and tyrphostin (a tyrosine kinase inhibitor), respectively. 3. Arginine-vasopressin-induced DNA synthesis was completely abolished in confluent cells, whereas [3H]inositol phosphate formation was only reduced. The presence of 12-O-tetradecanoylphorbol 13-acetate markedly decreased arginine-vasopressin-induced [3H]thymidine incorporation in fibroblasts from spontaneously hypertensive rats and was without effect in fibroblasts from Wistar-Kyoto rats. Tyrphostin abolished arginine-vasopressin-induced [3H]thymidine incorporation in a dose-dependent manner and did not affect the formation of inositol phosphates. 4. These results indicate that phospholipase C activation is not sufficient for arginine-vasopressin-induced mitogenesis. They also suggest that (i) tyrosine kinase activation is a necessary step in the transduction of the arginine-vasopressin mitogenic signal, and (ii) protein kinase C participates in the increased mitogenic potency of arginine-vasopressin in spontaneously hypertensive rats.

Animals↗
PubMed2003

Lipopolysaccharide endotoxin potentiates the effect of osmotic stimulation on vasopressin synthesis and secretion in the rat hypothalamus.

Vasopressin secreted by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei is essential for water balance. In this study, we examined magnocellular neurone responses to osmotic stimulation in vehicle-injected controls or rats receiving an intraperitoneal (i.p.) injection of 250 microg/100 g of lipopolysaccharide (LPS), 3 h or 6 h earlier. LPS injection had no effect on plasma vasopressin concentrations in control rats but it caused marked and transient potentiation of the responses to a single i.p. injection of hypertonic saline (five- and two-fold, 3 and 6 h after LPS, respectively). The enhancement of plasma vasopressin responses was independent of plasma sodium concentrations or changes in blood pressure. Basal vasopressin mRNA expression in the paraventricular and supraoptic nuclei decreased slightly 6 h after LPS injection, without changes in vasopressin transcription as indicated by vasopressin heteronuclear (hn) RNA levels. Parvocellular neurones showed expected increases in vasopressin hnRNA expression following LPS injection and a further increase after i.p. hypertonic saline injection (due to the painful component). In contrast to magnocellular vasopressin mRNA expression, the effects of LPS and hypertonic saline injections in parvocellular neurones were additive and not synergistic. Light microscopic immunohistochemical examination revealed an increase in size of vasopressin but not oxytocin axonal terminals in the neural lobe 3 h after LPS injection. Osmotic stimulation caused marked depletion of vasopressin immunoreactivity in axonal terminals of the neural lobe in both control and LPS-pretreated rats. The changes in vasopressin axon terminals were accompanied by induction of interleukin (IL)-1 beta and IL-6 in the posterior pituitary. The data show that endotoxemia causes morphological and functional alterations of the hypothalamic neurohypophyseal system, resulting in facilitation rather than inhibition of vasopressin synthesis, and secretion in response to osmotic stimulation.

Animals↗
PubMed1992

Vasopressin gene transcripts in mineralocorticoid hypertension: an in situ study.

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

Animals↗
PubMed2003

Circulating vasopressin levels in septic shock.

OBJECTIVE: To assess the frequency of vasopressin deficiency in septic shock. DESIGN: Prospective cohort study. SETTING: Intensive care unit at Raymond Poincaré University Hospital. PATIENTS: A cohort of 44 patients who met the usual criteria for septic shock for < 7 days. A second cohort of 18 septic shock patients were enrolled within the first 8 hrs of disease onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: General demographics, severity scores, vital signs, standard biochemical data, and circulating vasopressin levels were systematically obtained at baseline in the two cohorts. Vasopressin deficiency was defined by a normal plasma vasopressin level in the presence of a systolic blood pressure of <100 mm Hg or in the presence of hypernatremia. Baroreflex sensitivity was systematically evaluated in patients of the first cohort when vasopressin deficiency was noted. In the second cohort of patients, plasma levels of vasopressin were obtained at baseline, 6, 24, 48, and 96 hrs after shock onset. In the first population, plasma vasopressin levels were inversely correlated to the delay from shock onset. Fourteen patients had relative vasopressin deficiency: 12 patients had systolic blood pressure <100 mm Hg, with impaired baroreflex sensitivity in four, and three patients had hypernatremia. In the second population, only two patients had relative vasopressin deficiency. The plasma levels of vasopressin significantly decreased over time (p < 10-3). CONCLUSIONS: Plasma vasopressin levels are almost always increased at the initial phase of septic shock and decrease afterward. Relative vasopressin deficiency is seen in approximately one-third of late septic shock patients.

Analysis of Variance↗
PubMed2004

Vasopressin during cardiopulmonary resuscitation: a progress report.

OBJECTIVE: In patients undergoing cardiopulmonary resuscitation, circulating endogenous vasopressin concentrations were significantly higher in successfully resuscitated patients than in patients who died. These observations have prompted several investigations to assess the role of vasopressin to improve cardiopulmonary resuscitation management. DESIGN: Literature review. RESULTS: In the cardiopulmonary resuscitation laboratory, vasopressin improved vital organ blood flow, cerebral oxygen delivery, the probability of restoring spontaneous circulation, and neurologic recovery better than epinephrine. In pediatric preparations with asphyxia, epinephrine was superior to vasopressin, whereas in both pediatric pigs with ventricular fibrillation and adult porcine models with asphyxia, combinations of vasopressin and epinephrine proved to be highly effective. In addition, vasopressin enabled short- and long-term survival in a porcine model of uncontrolled hemorrhagic shock. In a recently published European, multiple-center trial, 1,219 adult patients with out-of-hospital cardiac arrest were randomized to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine followed by additional epinephrine if needed. The clinical study did not confirm laboratory data showing vasopressin to be more effective than epinephrine in ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine was more effective than epinephrine alone in the treatment of refractory cardiac arrest. CONCLUSIONS: According to new data from the European vasopressin study, we suggest, first, the administration of 1 mg of epinephrine, followed alternately by 40 IU of vasopressin and 1 mg of epinephrine every 3 mins in adult cardiac arrest victims, regardless of the initial electrocardiographic rhythm.

Advanced Cardiac Life Support↗
PubMed2004

Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.

Adrenergic beta-Agonists↗
PubMed2000

Regulation of vasopressin V1b receptors in the anterior pituitary gland of the rat.

Vasopressin secreted by parvocellular neurones of the hypothalamic paraventricular nucleus modulates pituitary adrenocorticotrophic hormone (ACTH) secretion by acting upon vasopressin V1b type receptors in the pituitary corticotroph coupled to phospholipase C. Regulation of V1b receptors contributes to the adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress, as evidenced by the correlation between vasopressin receptor number and pituitary ACTH responsiveness. V1b receptor upregulation during chronic stress is associated with elevated circulating glucocorticoids and vasopressin expression in parvocellular neurones, suggesting that these factors control V1b receptor expression. Removal of circulating glucocorticoids by adrenalectomy causes sustained vasopressin receptor downregulation, but reduces V1b receptor mRNA only transiently. The latter effect is not mediated by increased corticotrophin-releasing hormone (CRH) and vasopressin release, since it is not prevented by lesions of the hypothalamic paraventricular nucleus. Adrenalectomy causes sustained V1b receptor loss in Brattleboro rats, which lack hypothalamic vasopressin, suggesting that vasopressin mediates V1b receptor mRNA recovery. Exogenous glucocorticoid administration downregulates pituitary vasopressin binding but increases V1b receptor mRNA and facilitates coupling of the receptor to phospholipase C, effects which may contribute to the refractoriness of vasopressin actions to glucocorticoid feedback. The lack of parallelism between changes in pituitary vasopressin binding and V1b receptor mRNA levels during manipulation of the HPA axis indicates that V1b receptor content depends on post-transcriptional mechanisms rather than steady-state V1b receptor mRNA levels. These studies suggest that interaction between glucocorticoids and vasopressin plays an important role in regulating V1b receptor mRNA expression during alterations of the HPA axis. In addition, the recent characterization of a major part of the V1b receptor gene provides a basis for studying the molecular mechanisms regulating the V1b receptor.

Animals↗
PubMed1996

Endothelium-dependent and NO-mediated desensitization to vasopressin in rat aorta.

1. The present study was performed to characterize the tachyphylaxis of rat aortae to vasopressin. Isometric tension generated by rat thoracic aorta sliced in 4 mm rings, was recorded. 2. Tension generated by intact rings increased with cumulative additions of vasopressin up to 10 nM (1.51 +/- 0.15 g). After this concentration, most rings lost their tension and relaxed to 1.09 +/- 0.17 g (P < 0.001) despite further addition of vasopressin. This tachyphylaxis was not observed in endothelium-denuded rings (from 2.87 +/- 0.12 g to 2.68 +/- 0.17 g). 3. Repeated administrations of supramaximal concentration (100 nM) of vasopressin confirmed an enhanced desensitization in intact rings, compared to endothelium-denuded rings. No desensitization to phenylephrine was observed in intact or in endothelium-denuded rings. 4. Dose-response curves to a V1 receptor agonist, [Phe2, Ile3, Orn8]-vasopressin, and to a V2 receptor agonist, [deamino-Cys1,D-Arg8]-vasopressin, were performed in intact preparations. An increase in tension, followed by a desensitization was observed with the V1 receptor agonist. In contrast, the V2 receptor agonist did not induce any response. 5. Pretreatment of intact aortic rings with the cyclo-oxygenase inhibitor, diclofenac (1 microM), did not prevent the desensitization to vasopressin. In contrast, NO synthase inhibition with NG-nitro-L-arginine (30 microM) resulted in an attenuated desensitization to vasopressin in intact rings (from 2.46 +/- 0.17 to 2.25 +/- 0.22 g, NS). 6. To confirm the involvement of NO, endothelium-denuded rings were pretreated with sodium nitroprusside (SNP). At a concentration of 10 nM, SNP induced a desensitization to vasopressin comparable with that observed in intact rings. 7. Pretreatment of endothelium-denuded rings with 8-bromo-cyclic GMP (100 microM) reduced maximum contraction to vasopressin without producing any desensitization. In contrast, guanylate cyclase inhibition with either LY 83,583 (10 microM) or methylene blue (10 microM) blocked completely the desensitization of intact rings to vasopressin. 8. The results suggest that the endothelium-dependent tachyphylaxis to vasopressin is due to rapid desensitization and is mediated by NO. However, it is unclear whether this effect of NO involves cyclic GMP.

Animals↗
PubMed1984

Natriuretic response of the rat to plasma concentrations of arginine vasopressin within the physiological range.

The relationship of plasma vasopressin concentrations in the physiological range to renal electrolyte excretion was investigated. Unanaesthetized rats, when normally hydrated, were found to have a plasma vasopressin concentration of 1.13 +/- 0.15 mu u./ml. 16 h water deprivation raised this to 1.98 +/- 0.21 mu u./ml. Inactin-anaesthetized rats infused with 0.45% NaCl had a plasma vasopressin concentration of 1.19 +/- 0.18 mu u./ml. Administration of synthetic arginine vasopressin at 6 and 24 mu u./min raised plasma vasopressin levels to 1.88 +/- 0.17 and 4.26 +/- 0.43 microunits./ml respectively. In addition to the expected antidiuresis, vasopressin at a rate of 6 microunits./min also produced a highly significant increase in Na+ excretion from 8.9 +/- 0.6 to 10.5 +/- 0.6 mumol/min and Cl- excretion from 9.1 +/- 0.7 to 10.5 +/- 0.7 mumol/min. At 24 microunits./min it produced larger increases in Na+ and Cl- excretion. Inactin-anaesthetized hypophysectomized rats infused with 0.45% NaCl had a plasma vasopressin concentration of only 0.17 +/- 0.04 microunits./ml. Administration of vasopressin at 6 and 24 microunits./ml raised plasma vasopressin levels in these animals to 0.63 +/- 0.17 and 2.20 +/- 0.11 microunits./ml respectively. Hypophysectomized rats failed to exhibit a natriuresis in response to the lower dose of vasopressin, despite exhibiting an undiminished antidiuresis. The failure of the natriuresis may be related to the lower plasma vasopressin concentration achieved. It is concluded that in the rat plasma vasopressin concentrations within the physiological range do influence Na+ and Cl- excretion by the kidney as well as controlling urine flow rate.

Animals↗
PubMed1987

Osmoregulation and control of vasopressin secretion in healthy humans.

The functional characteristics of osmoregulated vasopressin secretion can be defined in terms of an osmotic threshold for its release and a sensitivity of the osmoreceptor and vasopressin-secreting unit. Osmotically stimulated thirst has features similar to osmoregulated vasopressin. There are wide individual variations in the functional characteristics of both thirst and vasopressin release in healthy humans, probably genetic in origin. The influence of aging appears to enhance the sensitivity of vasopressin secretion but blunt thirst appreciation. Yet in many physiological situations changes in osmoregulated vasopressin release and thirst occur in parallel. The fall in plasma osmolality associated with human pregnancy is accounted for entirely by a lowering of the osmotic thresholds for thirst and vasopressin release. Similar but less marked alterations accompany the ovulatory luteal phase of the menstrual cycle. A major nonosmotic stimulus to vasopressin secretion is hypotension and/or hypovolemia, mediated by high- (carotid sinus) and low- (left atrial) pressure receptors. Circulating catecholamines influence the release of vasopressin by alpha- and beta-adrenergic pathways. Drinking by hypertonic humans provides immediate reduction in thirst and vasopressin secretion probably mediated by pathways from the oropharynx. The modest but variable rise in plasma vasopressin in response to hypoglycemia appears to be due to cellular neuroglycopenia and is independent of parasympathetic pathways. Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.

Drinking↗
PubMed1991

Vasopressin mRNA expression in individual magnocellular neuroendocrine cells of the supraoptic and paraventricular nucleus in response to water deprivation.

Vasopressin neuroendocrine function involves the regulation of both secretion and synthesis from magnocellular neuroendocrine cells but the coordination of these two processes is poorly understood. To explore the temporal relationship between physiological stimulation and vasopressin mRNA levels we measured vasopressin mRNA content within individual magnocellular neurons of the supraoptic and paraventricular nucleus during the course of water deprivation. Analysis of autoradiographic silver grain densities from in situ hybridization of an [125I]dCTP-labeled oligonucleotide specific for vasopressin mRNA revealed a wide variety of resting vasopressin mRNA levels and differential responses to water deprivation in the magnocellular neuroendocrine cells. During water deprivation, the vasopressin mRNA content of the paraventricular nucleus increases rapidly and with shorter latency and greater incremental response than the supraoptic nucleus. Double-labeling experiments with combined in situ hybridization and immunocytochemistry identified a population of vasopressin immunoreactive cells which maintain very low basal levels of vasopressin mRNA. The location of these cells correlates with the location of increased silver grain densities during water deprivation. One subset of vasopressin magnocellular neurons failed to show high levels of vasopressin mRNA, indicating that all cells are not equally responsive to water deprivation. These patterns of vasopressin mRNA expression suggest the presence of functional subpopulations of vasopressin neuroendocrine cells which may reflect stimulus-specific patterns of afferent input to the supraoptic and paraventricular nucleus.

Animals↗
PubMed1995

Identification of vasopressin mRNA in rat aorta.

We have reported previously that several blood vessels of the rat and cow contain immunoreactive vasopressin and further suggested that this peptide might be produced locally. To provide additional support for this hypothesis, we conducted the present study to determine whether mRNA for arginine vasopressin is also present in blood vessels. Ribonuclease protection analysis of total RNA isolated from rat hypothalamus and aorta revealed the presence of arginine vasopressin message in both tissues but not in RNA isolated from liver, a tissue devoid of vasopressin. Subsequent comparison of the autoradiographic intensities of the signals in these two tissues indicated that vasopressin message was 100- to 1000-fold lower in aorta. Additional studies showed that RNA isolated from endothelium-denuded vessels contained levels of arginine vasopressin message similar to those in intact vessels, indicating that endothelium was not a major source of this message. These data were substantiated by further studies using a vasopressin radioimmunoassay, which showed that vasopressin peptide levels in intact and endothelium-denuded vessels did not differ. Thus, the present study showed that rat aorta contains arginine vasopressin mRNA as well as the vasopressin peptide and that both the message and the peptide are contained in nonendothelial structures. However, the data do not rule out endothelium as a possible source of vasopressin. These studies add further support to the hypothesis that blood vessels are capable of producing vasopressin.

Animals↗
PubMedDate not supplied

Contribution of vasopressin to hypertension.

The contribution of vasopressin to the hypertensive process has been examined in a number of models of hypertension. Vasopressin is essential for the production of DOC-salt hypertension in the rat, It is likely that vasopressin is required in the early stages of this model of hypertension for its antidiuretic activity and contributes to the later stages of the hypertension as a pressor agent. Vasopressin secretion is increased in SHR, but there may be some differences between the SHR and stroke-prone SHR strains. The pressor action of vasopressin appears to be important in the stroke-prone SHR with well-established hypertension, but not in the young SHR. Vasopressin secretion is greater in Dahl S rats on a high salt diet than in similarly treated R rats. Blockade of vasopressin's pressor activity failed to lower blood pressure in these S rats, unless they were pretreated with captopril. There is insufficient information to determine whether vasopressin has a role in the hypertension in NZGH rats. Vasopressin appears to function as a pressor agent in some, but not all, rats with two-kidney, one clip hypertension. Although vasopressin is not essential for the production of one-kidney, one clip hypertension, it apparently contributes to the hypertension by virtue of its antidiuretic activity. Vasopressin secretion is elevated in partial nephrectomy-salt hypertension, and here, too, it is needed for its antidiuretic action. The question of whether vasopressin secretion is elevated in human essential hypertension is controversial, and its role remains to be determined.

Animals↗
PubMed2003

Low-dose vasopressin in the treatment of septic shock in sheep.

After induction of cecal perforation, 20 anesthetized sheep were randomized to be treated, when arterial blood pressure fell below 75 mm Hg, with vasopressin (fixed dose of 0.02 U/minute), norepinephrine (0.5-5 microg/kg/minute titrated to maintain mean arterial pressure between 75 and 85 mm Hg), vasopressin + norepinephrine (vasopressin at fixed dose 0.01 U/minute plus norepinephrine titrated as for norepinephrine only group), or no vasopressor (Ringer's lactate [control]). Mean arterial pressure was well maintained in all treatment groups. Superior mesenteric arterial blood flow was significantly lower in the vasopressin + norepinephrine group than in the vasopressin group. Vasopressin alone or combined with norepinephrine limited the increase in blood lactate concentration and ileal PCO2-gap compared with control and norepinephrine groups. Urine output was higher in the vasopressin group than in control and norepinephrine groups. Survival time was longer in the vasopressin (30 +/- 6 hours) and vasopressin + norepinephrine (30 +/- 3 hours) groups than in the norepinephrine group (20 +/- 1 hours, p < 0.05) and in all treatment groups than in the control group (17 +/- 2 hours, p < 0.05). Tissue injury was less severe in the vasopressin and vasopressin + norepinephrine groups than in the others. In this clinically relevant model of septic shock due to peritonitis, vasopressin administration (alone or with norepinephrine) can prolong survival.

Animals↗
PubMed1975

Evidence for an in vivo antagonism between vasopressin and prostaglandin in the mammalian kidney.

These studies were undertaken to examine whether an antagonism between vasopressin and prostaglandin occurs in vivo in the mammalian kidney. All experiments were performed in steroid-replaced hypophysectonized dogs undergoing a water diuresis. In the first group of studied the effect of two consecutive intravenous doses (100 mU) of vasopressin was examined. The second dose of vasopressin was preceded by an injection of the carrier solution for solubilizing indomethacin or neclofenamate. No enhancement of the antidiuretic effect of the second dose of vasopressin was observed as urinary osmolality (Uosm) increased from 92 +/- 5 to 252 +/- 18 mosmol/kg H2O (P less than 0.0001) after the first dose and from 109 +/- 8 to 209 +/- 10 mosmol/kg H2O (P less than 0.001) after the second dose of vasopressin. In another group of studies the second dose of vasopressin was preceded by the administration of a potent inhibitor of prostaglandin synthesis, indomethacin (2 mg/kg). The Uosm increased from 93 +/- 9 to 244 +/- 33 mosmol/kg H2O (P less than 0.001) after the first dose of vasopressin, but after the second dose of vasopressin the Uosm increased to a significantly greater degree from 106 +/- 14 to 702 +/- 69 mosmol/kg H2O (P less than 0.001). In a third group of studies the antidiuretic effect of the same 100-mU dose of vasopressin was examined before and after the administration of meclofenamate (2 mg/kg), an inhibitor of prostaglandin synthesis which is chemically dissimilar from indomethacin. Uosm increased from 83+/-7 to 216+/-16 mosmol/kg H2O (P less than 0.001) after the first dose and from 101 +/- 8 to 734 +/- 86 mosomol/kg H2O (P less than 0.001) after the second dose of vasopressin. As in the indomethacin studies this enhancement in the antidiuretic effects of vasopressin after inhibition of prostaglanding synthesis was highly significant (P less than 0.001). These results therefore implicate a physiological role of prostaglandin in modulating the hydroosmotic effect of vasopressin in the mammalian kidney.

Animals↗
PubMed2001

Physiology of vasopressin relevant to management of septic shock.

Vasopressin is emerging as a rational therapy for the hemodynamic support of septic shock and vasodilatory shock due to systemic inflammatory response syndrome. The goal of this review is to understand the physiology of vasopressin relevant to septic shock in order to maximize its safety and efficacy in clinical trials and in subsequent therapeutic use. Vasopressin is both a vasopressor and an antidiuretic hormone. It also has hemostatic, GI, and thermoregulatory effects, and is an adrenocorticotropic hormone secretagogue. Vasopressin is released from the axonal terminals of magnocellular neurons in the hypothalamus. Vasopressin mediates vasoconstriction via V1-receptor activation on vascular smooth muscle and mediates its antidiuretic effect via V2-receptor activation in the renal collecting duct system. In addition, vasopressin, at low plasma concentrations, mediates vasodilation in coronary, cerebral, and pulmonary arterial circulations. Septic shock causes first a transient early increase in blood vasopressin concentrations that decrease later in septic shock to very low levels compared to other causes of hypotension. Vasopressin infusion of 0.01 to 0.04 U/min in patients with septic shock increases plasma vasopressin levels to those observed in patients with hypotension from other causes, such as cardiogenic shock. Increased vasopressin levels are associated with a lesser need for other vasopressors. Urinary output may increase, and pulmonary vascular resistance may decrease. Infusions of > 0.04 U/min may lead to adverse, likely vasoconstriction-mediated events. Because clinical studies have been relatively small, focused on physiologic end points, and because of potential adverse effects of vasopressin, clinical use of vasopressin should await a randomized controlled trial of its effects on clinical outcomes such as organ failure and mortality.

Animals↗
PubMed1984

Release of oxytocin and vasopressin by magnocellular nuclei in vitro: specific facilitatory effect of oxytocin on its own release.

The release of endogenous oxytocin and vasopressin by rat paraventricular and supraoptic nuclei in vitro during a 10-min period, 30 min after beginning the incubation, was measured radioimmunologically. Mean basal hormone release per 10 min and per pair of nuclei was: 128.4 +/- 12.4 (S.E.M.) pg vasopressin (n = 15) and 39.0 +/- 3.0 pg oxytocin (n = 66) for supraoptic nuclei from male rats; 273.9 +/- 42.6 pg vasopressin (n = 11) and 34.2 +/- 3.5 pg oxytocin (n = 15) for supraoptic nuclei from lactating rats; 70.0 +/- 8.6 pg vasopressin (n = 52) and 21.8 +/- 1.3 pg oxytocin (n = 68) for paraventricular nuclei from male rats; 59.1 +/- 8.6 pg vasopressin (n = 10) and 27.0 +/- 4.6 pg oxytocin (n = 16) for paraventricular nuclei from lactating rats. In male and lactating rats, both nuclei contained and released more vasopressin than oxytocin. For oxytocin alone, the paraventricular nucleus of male rats contained and released significantly less hormone than the supraoptic nucleus. This difference was not apparent in lactating rats. For vasopressin alone, the paraventricular nucleus contained and released significantly less hormone than the supraoptic nucleus in both male and lactating rats. When the hormone released was calculated as a percentage of the total tissue content the release was about 0.9% for oxytocin from both nuclei in male and lactating rats and also for vasopressin in lactating rats, but was only about 0.5% for vasopressin from both nuclei in male rats. The influence of oxytocin and analogues of oxytocin (including one antagonist) upon the release of oxytocin and vasopressin was studied. Adding oxytocin to the incubation medium (0.4-4 nmol/1 solution) induced a dose-dependent rise in oxytocin release from both nuclei of male or lactating rats. A 4 nmol/l solution of isotocin had a similar effect to a 0.4 nmol/l solution of oxytocin, but arginine-vasopressin never affected basal release of oxytocin. In no case was vasopressin release modified. An oxytocin antagonist (1 mumol/l solution) significantly reduced basal oxytocin release and blocked the stimulatory effect normally induced by exogenous oxytocin, as did gallopamil hydrochloride (D600, 10 mumol/l solution), a Ca2+ channel blocker, or incubation in a Ca2+-free medium. These findings are discussed in relation to the literature on the central effects of neurohypophysial peptides. It may be concluded that the regulatory role of endogenous oxytocin in the hypothalamus on the milk-ejection reflex could result from its local release in the extracellular spaces of magnocellular nuclei.

Animals↗
PubMed2004

[Vasopressin and its analogues in the therapy of shock].

Hemodynamic support during the circulatory failure with vasodilation, most frequently during the septic shock, is based on volume recovery and administration of inotropic drugs. If such therapy is not sufficient, vasoconstriction drugs are subsequently or parallel added to maintain the perfusion pressure. As a standard therapy, norepinephrine or other catecholamines with alpha-adrenergic effect are used in rising doses. Some patients do not respond to such therapy with desired hemodynamic changes--they develop catecholamine resistant shock. Because of serious side effects of high doses of catecholamines, alternative vasopressors are necessary. Vasopressin, antidiuretic hormone, has in physiological conditions only minimal effect of the vascular tone. During hypovolemia its concentration rises and it may significantly contribute to the maintenance of arterial pressure by vasoconstriction. Contrary to it, during septic shock the levels of vasopressine are very low and vasodilation clinically dominates. At the same time, the septic shock is accompanied by an increased sensitivity to vasopressin administration. In a critical shock a serious deficit of endogenous vasopressin is expected. At present several pilot studies with vasopressine administration in septic shock exist in literature describing beneficial effect of vasopressin on hemodynamic parameters. Such comparatively low doses have no side effects on perfusion and function of body organs. Terlipressin, which is available in Czech Republic, is a synthetic analogue of vasopressin with extended effect. Its intermittent administration is used for the treatment of portal hypertension complications. Terlipressin in animal model of septic shock has similarly beneficial effects as vasopressin. High doses of Terlipressin have, similarly to vasopressin, adverse effects on pulmonary circulation and other systems. Till present, only casuistic experience has been published with low doses of Terlipressin in the treatment of septic shock resistant to catecholamines, which has shown similar effects to vasopressin. In shock states with the deficit of endogenous vasopressin, which are resistant to high doses of catecholamines, administration of vasopressin analogues represents a new perspective therapy. The treatment should be studied from the point of morbidity and mortality. A careful approach has to be used in septic patients with pre-existing obliterative vassal disease.

Animals↗