Role Of Vasopressin Research Articles

Vasopressin contributes to maintenance of arterial blood pressure in dehydrated baboons

This study primarily sought to determine whether the role of vasopressin (VP) in maintenance of arterial blood pressure is enhanced in awake, chronically instrumented baboons after 68-72 h of dehydration. This question was approached by pharmacologically blocking vasopressin V1-receptors in euhydrated and dehydrated baboons with or without a normally functioning renin-angiotensin system (RAS). VP blockade during dehydration produced a rapidly occurring (within 5 min), statistically significant (P less than 0.05) decrease in mean arterial pressure (MAP) of 5 +/- 1 mmHg in the RAS-intact condition and an identical decline in MAP (5 +/- 1 mmHg) during blockade of the RAS by captopril, an angiotensin I-converting enzyme inhibitor. At 15 min after induction of VP blockade, heart rate was elevated by 9 +/- 2 beats/min in the RAS-intact condition and by 20 +/- 5 beats/min in the RAS-blocked condition. In addition, VP blockade in the dehydrated state produced small and equal increases in hindlimb vascular conductance in RAS-intact and RAS-blocked conditions. None of these cardiovascular changes were produced by VP blockade in the euhydrated state. RAS blockade produced modest declines in MAP in both hydration states, but the fall was larger by 7 +/- 4 mmHg in the dehydrated state. Thus both VP and the RAS contribute to the maintenance of arterial blood pressure during dehydration in the conscious baboon.

Role of vasopressin in cardiovascular regulation.

Role of vasopressin in cardiovascular regulation.

Regional hemodynamic responses to adrenoceptor antagonism in conscious rats.

Changes in blood pressure and renal, mesenteric, and hindquarters vascular resistances were measured in conscious Long-Evans and Brattleboro (vasopressin-deficient) rats in response to sequential, continuous administrations of prazosin and idazoxan in the absence or presence of ICI 118551 (beta 2-adrenoceptor antagonist) or propranolol. The large transient hypotensions elicited by prazosin and, subsequently, by idazoxan were associated with renal and hindquarters vasodilatations in both strains of rat. In Brattleboro rats, prazosin also elicited mesenteric vasodilatation. Pretreatment with ICI 118551 reduced the initial hypotensive effects and hindquarters vasodilatations elicited by prazosin and idazoxan, but the hemodynamic effects of prazosin were not significantly affected by propranolol. These results are consistent with propranolol antagonizing beta 1-adrenoceptor-mediated effects on the heart and the renin-angiotensin system that act to offset a beta 2-adrenoceptor-mediated vasodilatation, which contributes to the effects elicited by alpha-adrenoceptor antagonism. Hemodynamic responses to captopril and d(CH2)5DAVP (in Long-Evans rats) in the presence of adrenoceptor antagonists were consistent with a major cardiovascular role of the renin-angiotensin system and a less overt role of vasopressin until the latter system was blocked.

Support of arterial blood pressure by major pressor systems in conscious dogs.

The roles of the autonomic nervous system, vasopressin, and angiotensin II in support of blood pressure were evaluated in seven conscious, resting dogs while hydrated or dehydrated. Mean arterial blood pressure (MAP) was monitored, and the dogs were given hexamethonium to block autonomic ganglia. Thirty minutes later, they were given captopril, and after another 30 min, a vasopressin V1 antagonist, d(CH2)5TyrMeAVP, was given. The order okf administration of captopril and d(CH2)5TyrMeAVP was alternated in different experiments. Hexamethonium had no effect on steady-state MAP in either hydrated or dehydrated dogs. In hydrated dogs, the average MAP was 100 mmHg; d(CH2)5TyrMeAVP decreased MAP by approximately 12 mmHg, and captopril decreased MAP by 24 mmHg. The magnitude of the effect of these two inhibitors was independent of the order of their administration. Dehydration doubled the effect of d(CH2)5TyrMeAVP on MAP but had no effect on the response to captopril. The results suggest that 1) autonomic function is not essential for maintenance of arterial blood pressure in resting dogs; 2) during autonomic ganglionic blockade, arterial blood pressure is supported by both angiotensin II and vasopressin; and 3) dehydration increases the role of vasopressin in control of blood pressure.

Compensatory pressor role of vasopressin following acute diuresis.

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

Role of vasopressin in experimental heart failure.

Neurohumoral vasoconstrictor systems are activated in heart failure and influence left ventricular function by modifying pre- and afterload. The renin-angiotensin system, sympathetic nerve activity and vasopressin have all been implicated as mechanisms of vasoconstriction. We investigated the vasoconstrictive action of vasopressin by blocking its vascular receptors by a specific antagonist in animal models of heart failure due to rapid right ventricular pacing in dogs and to aortocaval fistula, pulmonary stenosis and aortic stenosis in rats. In all animal models studied, we observed an inappropirately elevated secretion of vasopressin in association with a decreased plasma osmolality. We found only a small reduction of aortic pressure and peripheral vascular resistance following the vasopressin inhibitor. The renin-angiotensin system and sympathetic nerve activity were activated in all animal models. We injected teprotide in order to test the role of angiotensin in the regulation of peripheral vascular tone, and found a much greater decrease of blood pressure and peripheral vascular resistance than caused by the vasopressin antagonist. These experiments suggest that vasopressin and the renin system increase peripheral vascular tone in certain models of heart failure, and demonstrate a much greater importance for the renin system.

The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders

Perfusion of the peptide, arginine vasopressin (AVP), within the ventral septal area (VSA) of the brain of a number of species reduces fever but not normal body temperature. This antipyretic response appears to be mediated by AVP receptors of the V 1 subtype. Lesions of the VSA with kainic acid are associated with prolonged and enhanced fevers in rats. A role for endogenous AVP in fever suppression within the VSA comes from several types of experiments: (1) AVP release within the VSA is inversely correlated to fever height, (2) AVP antagonists or antiserum injected into the VSA prolong fever, (3) animals lacking endogenous AVP in the VSA (Brattleboro rat, long-term castrated rat) develop enhanced fevers. Electrical stimulation of the AVP-containing cell bodies of the bed nucleus of the stria terminalis (BST) orthodromically inhibits VSA neurons and also suppresses fever, the latter effect can be abolished with application of a V 1 antagonist to the VSA. lontophoretic studies indicate that AVP inhibits glutamatestimulated activity of thermoresponsive and other VSA neurons. AVP can also act in the VSA to cause severe motor disturbances, this action is receptor mediated and increases in severity upon sequential exposure to AVP. Because sites of action of the antipyretic and convulsive action of AVP are similar, and because animals lacking brain AVP display reduced convulsive activity, it is possible that AVP, released during fever, could be involved in the genesis of convulsive activity.

Sex difference in pressor responsiveness to vasopressin and baroreflex function in DOC-salt hypertensive rats

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

Vasoconstrictor Role of Vasopressin and Angiotensin in Experimental Aortic Stenosis in the Rat

The roles of vasopressin and angiotensin II in the regulation of peripheral vascular tone were investigated in control rats and in rats with chronic (15 weeks) aortic stenosis, by intravenous application of a specific antagonist to the vascular receptors of vasopressin and the angiotensin-converting enzyme inhibitor teprotide. The application of a Silver clip (0.6 mm) on the aorta ascendens produced a hemodynamically effective aortic stenosis with an increase in left ventricular weight (38%), a reduction in mean arterial pressure, cardiac index, and stroke volume index, and an increase in peripheral vascular resistance. In both groups of rats, a bolus injection of 30 micrograms of the vasopressin inhibitor d (CH2) 5 Tyr (Me) arginine vasopressin (AVP) showed an agonistic effect by increasing arterial pressure by 11 and 15 mm Hg, respectively, and no antagonistic effect in the control animals. In the rats with chronic aortic stenosis we observed a significant fall in blood pressure (4.1 +/- 5.5 mm Hg; p less than 0.05) and a reduction in peripheral vascular resistance of 6.3% (p less than 0.02). Stroke volume index and heart rate did not change. Most of the animals with aortic stenosis had inappropriately elevated plasma levels of vasopressin and increased levels of plasma renin concentration. The rats with aortic stenosis and inappropriately increased values of vasopressin showed significantly lower plasma osmolality, cardiac index, and stroke volume index and increased peripheral vascular resistance compared with the stenosed rats with a normal osmoregulation of vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Vasopressin in Regulation of Sodium Excretion

It has been proposed that arginine vasopressin (AVP) contributes to the regulation of renal sodium excretion by direct intrarenal actions, by neural-hormonal interactions, and via secondary effects of fluid volume retention. The present studies were designed to determine the extent to which the natriuretic effects of AVP are secondary to volume expansion. Three groups of dogs were studied: the first was infused with AVP for 2 weeks in amounts that increased plasma levels from 3 to 15 pg/mL, while water intake was maintained constant by intravenous (iv) water infusion. The second group received the same amount of AVP and was permitted to drink ad libitum. The third group was infused with the same amount of AVP, while total body weight and volume were maintained at a constant level by use of an electronically servo-controlled water infusion system. The results showed a large increase in total body weight (+1.5 kg) and arterial pressure (mean arterial pressure (MAP); +40 mm Hg) in dogs receiving a fixed water intake. This was accompanied by a continuing natriuresis over a 2-week period and severe hyponatremia (115 mEq/L). Dogs allowed ad libitum drinking retained much less fluid (+0.5 kg). MAP was not significantly elevated, and natriuresis did not occur in this group, but hyponatremia was observed (130 mEq/L), and plasma renin activity (PRA) was suppressed. Servo-controlled dogs exhibited no change in MAP, plasma sodium, or PRA, and only a small (-15 mEq) natriuresis occurred on day 1 of AVP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactive vasopressin and oxytocin in hypothalamo-hypophysial portal blood of the Brattleboro and Long-Evans rat: effect of adrenalectomy and dexamethasone.

Immunoreactive vasopressin and oxytocin were measured in the hypothalamo-hypophysial portal blood of both Long-Evans and homozygous Brattleboro rats. Adrenalectomy caused an increase in vasopressin immunoreactivity in portal blood in the Long-Evans strain, whilst administration of dexamethasone to these adrenalectomized animals resulted in a reduction in portal vasopressin immunoreactivity to levels below those seen in sham-operated animals. This vasopressin immunoreactivity co-eluted with synthetic vasopressin on high-pressure liquid chromatography (HPLC), and diluted in parallel in radio-immunoassay. In Brattleboro rats, however, although vasopressin-like immunoreactivity was detected, the portal concentration did not vary with the adrenal status of the animal, nor did it show the characteristics of standard vasopressin on HPLC or in immunoassay. Oxytocin was present in the portal blood of both Long-Evans and Brattleboro rats at similar very high concentrations, but did not vary in response to adrenalectomy. These results are consistent with a role for vasopressin, but not oxytocin, in the hypothalamic response to adrenalectomy and glucocorticoid feedback. Neither vasopressin immunoreactivity nor oxytocin appear to subserve this role in the homozygous Brattleboro rat.

The role of vasopressin in the regulation of haemostatic function in man—fact or fiction?

The role of vasopressin in the regulation of haemostatic function in man—fact or fiction?

Antagonists of the antidiuretic activity of vasopressin.

Competitive antagonists of the antidiuretic (ADH) activity of vasopressin were first described some six years ago. When studied in vitro, ADH antagonists displace vasopressin from specific renal binding sites and antagonize, in a competitive fashion, vasopressin stimulation of adenylate cyclase and transepithelial water, salt, and urea fluxes. When studied in vivo, the ADH antagonists increase renal water excretion and antagonize, in a competitive fashion, the ADH activity of vasopressin. Marked species heterogeneity is apparent with ADH antagonists in vivo, and inconsistencies between in vitro and in vivo findings within the same species are reported. Other renal responses associated with administration of ADH antagonists include changes in renal hemodynamics and renal salt and urea excretion. The effects on salt excretion appear to be limited to those species in which vasopressin stimulation of epithelial salt reabsorption has been demonstrated. In summary, the role of vasopressin as the principal factor regulating renal water handling is supported by experience with ADH receptor antagonists. However, that experience also indicates the emerging significance of autocoids, and other synergistic factors, to affect ADH receptor/effector mechanisms and to modulate renal ADH responses.

Neuropeptides and functional neuroteratology

Publisher Summary This chapter provides evidence that many neuropeptides actually influence brain development and those abnormalities in the levels of neuropeptide may lead to permanent dysfunction of the nervous system in particular, to functional neuroteratology. The chapter provides particular emphasis on the possible role of vasopressin in normal and abnormal development. Nowadays, it is clear that neurotransmission in the nervous system is brought about by a variety of endogene substances, including nucleotides, acetylcholine, amino acids, catecholamines, serotonin, histamine and neuropeptides. The number of neuropeptides outnumbers, by far, the other more “classical” neurotransmitters. Some neuropeptides can be demonstrated immunochemically early in rat development. Data available for catecholamines and serotonin demonstrating the presence of these neurotransmitter compounds prior to the first peak of neurogenesis in which the aminergic and serotonergic neurons are born are lacking for the neuropeptides. Neuropeptides and their agonist and antagonist analogues are, therefore, potential neuroteratogens, which, upon perinatal use, can alter the brain in a subtle but long-lasting way. This aspect should also alert clinicians who intend to use these compounds therapeutically in pregnant mothers and young children.

Regulation of vasopressin and oxytocin release in vitro.

Numerous studies have demonstrated a role for vasopressin (VP) and oxytocin (OT) in the regulation of adrenocorticotropin (ACTH) release. Both VP and OT release potentiate the effect of corticotropin releasing factor (CRF) on ACTH release (1), and they are present in portal plasma at the concentration required for this action (2). VP and CRF are co-localized in parvicellular neurons in the paraventricular nucleus which project to the median eminence (3–6), and both of these hormones are released from the isolated median eminence following depolarization (7). Thus, this appears to be one source of VP for regulation of ACTH release. OT is also present in some CRF neurons (8), but it has not been established whether these neurons project to the median eminence. Thus, it is not clear which neurons release OT into the portal circulation, but there are OT fibers in the external zone of the median eminence (9) suggesting a specific projection for control of the anterior pituitary.

Involvement of Vasopressin in the Down-Regulation of Pituitary Corticotropin-Releasing Factor Receptors after Adrenalectomy

The role of vasopressin (VP) in the regulation of pituitary corticotropin-releasing factor (CRF) receptors was studied by examining the effects of adrenalectomy and VP infusion on pituitary CRF receptors in genetically VP-deficient rats (di/di) and Long-Evans control rats. Binding studies with [125I]Tyr-ovine CRF in 30,000 X g anterior pituitary membrane-rich fractions revealed similar characteristics for the CRF receptors in Long-Evans and di/di rats, with Kd values of 2.4 +/- 0.6 and 1.9 +/- 0.2 nM, respectively, and receptor concentrations of 278 +/- 31 and 286 +/- 43 fmol/mg, respectively. Two days after adrenalectomy, the pituitary CRF receptor concentration decreased by 72 +/- 4.2% in Long-Evans rats, but by only 20.3 +/- 5.6% in di/di rats. CRF receptor affinity was unchanged after adrenalectomy (Kd = 1.7 +/- 0.5 nM; n = 8). To determine whether VP deficiency is responsible for the smaller decrease in CRF receptor in di/di rats, the effect of exogenous VP infusion (100 ng/min) by sc osmotic minipumps was studied in adrenalectomized di/di rats. Two days after adrenalectomy, pituitary CRF receptors were reduced by 21 +/- 8% in control di/di rats, whereas a 77.7 +/- 1.8% decrease was observed in VP-infused di/di rats, comparable to the effect of adrenalectomy in Long-Evans rats. VP infusion also caused a significant 35 +/- 2% decrease in CRF receptors in the pituitaries of sham-operated di/di rats, with no change in CRF receptor affinity. In Sprague-Dawley rats, VP or CRF infusion (100 ng/min) decreased pituitary CRF receptors by 14 +/- 1.9% and 46 +/- 3%, respectively. However, the combined infusion of both peptides caused a 65% +/- 4.2 decrease, similar to that observed after adrenalectomy. In vitro incubation of quartered pituitaries with VP or CRF for 4 h reduced CRF receptors by 23.1 +/- 8.2% and 38.2 +/- 3.8%, respectively, while simultaneous preincubation with both peptides was followed by a decrease of 55.3 +/- 5.3%. These findings indicate that increased hypothalamic release of VP contributes to the down-regulation of pituitary CRF receptors after adrenalectomy.

Responses of vasoactive hormones in congestive cardiac failure

Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.

Effect of vasopressin on electrical and contractile responses of vascular smooth muscles in animals of different ages

Most studies of the role of vasopressin in theregulation of cardiovascular function and the development of cardiovascular pathology have been devoted to an examination of changes in the central and regional hemodynamics [5, 6, ii]. Direct effects of the hormone on the vascular wall have been studied frankly insufficiently. The same can also be said of investigations into the effects of vasopressin at different ages. We know that systemic hemodynamic responses to vasopressin are modified in old age [3, 4]. However, changes in the functional state of vascular smooth-muscle cells (SMC) in old age have been inadequately studied.

The Role of Vasopressin in the Regulation of Fibrinolysis: Haemostatic Responses to Hypotension in the Absence of Adrenaline Release

The Role of Vasopressin in the Regulation of Fibrinolysis: Haemostatic Responses to Hypotension in the Absence of Adrenaline Release

The role of vasopressin on hemodynamic responce in the baroreceptor reflex in SHR

1) MAP decreased after AVP-A and it decreased further after C-6, 2) the elevation of MAP during BCD was suppressed after C-6 but not after AVP-A.3) BCD after AVP-A or C-6 elicited larger increase in PNE or PAVP than that of control BCD, respectively.The results suggest that sympatheric nervous system plays an important role in pathogenesis of hypertension of SHR and vasopressin plays a role in blood pressure homeostasis in case of sympathetic insufficiency.