pituitrin and argipressin--beta-mercapto-beta-beta-cyclopentamethylenepropionic-acid(1)-

We have previously shown that a chronic reduction in plasma vasopressin level slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribution of pressor (V1) and antidiuretic (V2) effects of vasopressin on progression. Male homozygous Brattleboro rats with hereditary central diabetes insipidus were submitted to 5/6 nephrectomy. They were divided into three groups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) or dDAVP (V2 effects). The third group served as control (CONT). The doses of AVP and dDAVP were chosen so as to produce urine osmolality similar to that observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. All three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fractional excretion of urea was markedly decreased and plasma urea concentration rose much more than that of creatinine. These results show that V2 but not V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression seen in dDAVP rats could indirectly result from the V2-mediated effects on the collecting duct resulting in a decreased efficiency of urea excretion, an increased intrarenal urea recycling, and a rise in plasma urea concentration. Both the toxic effects of urea and the recently demonstrated V2-mediated increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Creatinine; Diabetes Insipidus; Disease Models, Animal; Disease Progression; Kidney; Kidney Failure, Chronic; Male; Proteinuria; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Uremia; Vasopressins

Xeric-adaptation was studied during 28 days of total water deprivation (TWD) in Notomys alexis. Beyond 7 days, the initial reductions in body weight and increases in haematocrit, plasma renin and juxtaglomerular (JG) cell morphological activity returned to normal. Mus musculus showed similar changes at 7 days but could not be maintained thereafter. TWD decreased the blood pressure of Notomys but endogenous angiotensin and vasopressin did not support pressure to a greater extent than controls, as revealed by selective antagonists. The normal morphology of the JG apparatus in Notomys was similar to other rodents. Fluid volume and blood pressure maintenance during TWD in Notomys do not depend upon enhanced activities of the renin-angiotensin and antidiuretic hormonal systems.

Topics: Adaptation, Physiological; Animals; Arginine Vasopressin; Blood Pressure; Body Weight; Enalaprilat; Hematocrit; Juxtaglomerular Apparatus; Male; Mice; Mice, Inbred BALB C; Renin; Rodentia; Saralasin; Vasopressins; Water Deprivation

In order to investigate the central effect of endothelin-1 (ET-1) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular and renal function, either a high dose of ET-1 (3.5 ng/kg/min, HET-1) or a low dose (0.35 ng/kg/min, LET-1) was administered into the cerebral third ventricle in conscious rats. ET-1 increased the mean arterial blood pressure, but not heart rate, in a dose-related manner. LET-1 slightly stimulated AVP release, but not ANP release. HET-1 increased plasma AVP and ANP. Pretreatment with a V1-antagonist (TMeAVP) attenuated the blood pressure response to ET-1 and completely abolished increases in plasma ANP. Moreover, prazosin given i.v. completely prevented the residual pressure response. ET-1 did not significantly affect renal electrolytes and water handling. These results suggest that centrally administered ET-1 may increase the activity of the sympathetic nervous system and vasopressinergic neurons, resulting in an increase in blood pressure.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Dose-Response Relationship, Drug; Endothelins; Heart Rate; Hemodynamics; Injections, Intraventricular; Kidney; Male; Prazosin; Radioimmunoassay; Rats; Rats, Inbred Strains; Vasopressins

Vasopressin, like angiotensin, has both vasoconstrictor and fluid retaining properties and therefore may make an important contribution to the pathogenesis of low output congestive heart failure. The study aimed to examine the relative importance of the renin-angiotensin system and vasopressin in an animal model of heart failure.. The acute haemodynamic effects of vasopressin receptor blockade with a selective antagonist, d(CH2)5DAVP (AVPA) (30 micrograms.kg-1) and angiotensin converting enzyme inhibition with captopril (1 mg.kg-1) were compared. The effect of combined blockade (ie, vasopressin receptor antagonist + angiotensin converting enzyme inhibitor) was also examined.. Rabbits, 2.5-3.5 kg, with doxorubicin induced cardiomyopathy and heart failure (n = 20) were used. There were 15 controls.. Both AVPA and captopril produced significant increases in cardiac output (11% and 13% respectively) and falls in peripheral vascular resistance (21% and 17% respectively). Inhibition of the two vasoconstrictor systems was additive and resulted in a fall in peripheral vascular resistance to levels found in normal animals.. Vasopressin and angiotensin II make equal contributions to the raised peripheral vascular resistance observed in this model of heart failure. Vasopressin inhibition may be useful in the treatment of heart failure either alone or as an adjunct to angiotensin converting inhibition.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Captopril; Cardiac Output; Disease Models, Animal; Female; Heart Failure; Male; Rabbits; Vascular Resistance; Vasopressins

To determine the significance of vasopressin in cardiovascular and neurohormonal responses caused by centrally administered hypertonic NaCl, we examined the effects of a vasopressin antagonist on blood pressure, heart rate, plasma levels of catecholamines, cortisol and renin activity in anesthetized dogs. Intracerebroventricular (ICV) injections of 0.2 ml of 1.5 M NaCl increased mean arterial blood pressure (+29.7 +/- 3.0 mmHg, mean +/- SE), heart rate (+27.9 +/- 7.0 beats/min), plasma concentrations of vasopressin (+48.9 +/- 8.2 pg/ml), norepinephrine (+40.0 +/- 6.2 pg/ml), epinephrine (+231.4 +/- 21.4 pg/ml) and cortisol (+5.3 +/- 1.1 micrograms/dl) and decreased plasma renin activity (-2.0 +/- 0.4 ng/ml/hr). An intravenous vasopressin antagonist, d(CH2)5Tyr(Me)AVP, at a dose of 10 micrograms/kg, attenuated the pressor response and augmented the heart rate response to ICV 1.5 M NaCl. The vasopressin antagonist also augmented the change in plasma norepinephrine and significantly attenuated the responses of cortisol and renin. Baseline levels of these variables were not altered by the vasopressin antagonist except for an increase in renin activity. Two injections of hypertonic NaCl without any pretreatment produced similar cardiovascular and hormonal responses. These results suggest that vasopressin contributes not only to an increase in blood pressure, but also to changes in the sympathetic nervous system, the hypothalamo-adrenocortical axis and the peripheral renin-angiotensin system in response to a central sodium stimulus.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Dogs; Epinephrine; Heart Rate; Hemodynamics; Hydrocortisone; Injections, Intraventricular; Male; Neurotransmitter Agents; Norepinephrine; Renin; Saline Solution, Hypertonic; Vasopressins

We investigated the pressor sensitivities to vasopressin, angiotensin II, and methoxamine of intact and ganglion-blocked rats that had been treated 21 days earlier with streptozotocin or saline. No differences in blood pressure or heart rate responses to vasopressin or angiotensin II were found between the intact groups when these peptides were administered intravenously in equimolar doses. After ganglion blockade a significant enhancement in pressor responsiveness to both vasopressin and angiotensin II was observed in the control groups, but in the streptozotocin-treated animals no enhancement in pressor sensitivity to vasopressin was found. Furthermore, although a significant augmentation of the responses to angiotensin II was observed, it was smaller than that seen in the ganglion-blocked control group. Neither group showed enhanced pressor responsiveness to methoxamine. These results indicate that the previously observed diminished contributions from endogenous vasopressin and the renin-angiotensin system to blood pressure recovery following ganglion blockade in streptozotocin-treated rats may have been due, at least in part, to diminished pressor responsiveness.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Captopril; Diabetes Mellitus, Experimental; Heart Rate; Male; Methoxamine; Pentolinium Tartrate; Pressoreceptors; Rats; Rats, Inbred Strains; Renin; Vasopressins

Adult rats treated neonatally with guanethidine had normal arterial blood pressures, but these were more dependent on the renin-angiotensin system than in control animals. Antagonism of V1-receptors (with d(CH2)5DAVP) enhanced the depressor effects of captopril in guanethidine-treated animals, but blood pressure was unaffected by this manoeuvre in control animals. Although there is evidence that sympathetic efferent vasomotor function is abolished following the schedule of neonatal guanethidine treatment used, pentolinium had a hypotensive effect in the presence of d(CH2)5DAVP and captopril, indicating that the adrenal medulla could have been contributing to the maintenance of blood pressure. This is consistent with the finding of marked supersensitivity to exogenous adrenaline in guanethidine-treated rats.

Topics: Animals; Animals, Newborn; Arginine Vasopressin; Blood Pressure; Captopril; Epinephrine; Female; Guanethidine; Heart Rate; Infusions, Intravenous; Male; Pentolinium Tartrate; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Vasopressin; Renin-Angiotensin System; Vasopressins

Isosmotic volume depletion was induced by subcutaneous injection of 5 ml of polyethylene glycol (PEG; 20 M; 30%) in Long-Evans rats and in rats deficient in hypothalamic vasopressin (Brattleboro rats). In the PEG-treated Long-Evans rats, captopril caused a hypotension that was greater than that seen in saline-injected controls. Pretreatment with the vasopressin (V1 receptor) antagonist d(CH2)5DAVP did not, itself, cause a fall in blood pressure, but it enhanced the hypotensive effect of captopril in the PEG-treated Long-Evans rats. The PEG-treated Brattleboro rats had similar resting blood pressures to the PEG-treated Long-Evans rats, but in the former group, captopril caused a more profound and progressive hypotension than was seen in any of the present experimental regimes used in the Long-Evans rats. This suggests that, during hypovolemia induced by PEG, Brattleboro rats were either more dependent on the renin-angiotensin system for the maintenance of arterial blood pressure than were Long-Evans rats treated acutely with a vasopressin (V1) receptor antagonist or less able to recruit sympathoadrenal mechanisms to compensate for the sudden loss of the renin-angiotensin system.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Blood Pressure; Blood Volume; Captopril; Cardiovascular System; Male; Pentolinium Tartrate; Polyethylene Glycols; Rats; Rats, Brattleboro; Rats, Inbred Strains; Vasopressins

1. Plasma volumes and cardiovascular status were assessed in rats with a congenital deficiency in hypothalamic vasopressin (Brattleboro strain) and in the parent strain (Long Evans), in water-replete and water-deprived states. 2. Water-replete Brattleboro rats were not hypovolaemic; water deprivation (14 h in Brattleboro rats, 53 h in Long Evans rats) produced similar percentage reductions in plasma volumes in the two groups. 3. In the water-replete state, cardiovascular variables were similar in Long Evans and Brattleboro rats. Inhibition of ganglionic transmission (with pentolinium) or of the renin-angiotensin system (with captopril), separately, did not have a greater effect on blood pressure in Brattleboro rats than in Long Evans rats. Recovery from hypotension caused by pentolinium was characterized by large swings in blood pressure in both groups of rats. These pressor episodes were abolished by administration of captopril to Brattleboro rats. After administration of pentolinium and captopril to Long Evans rats there was a substantial, although intermittent, recovery in blood pressure that was abolished by an antagonist of the cardiovascular actions of vasopressin. 4. In the water-deprived state, blood pressures were similar in Long Evans and Brattleboro rats; both groups showed an elevation in diastolic blood pressure relative to the water-replete state. After administration of pentolinium, there was a more marked recovery in blood pressure than was seen in the water-replete state. Administration of captopril alone had a slightly greater effect on blood pressure in Long Evans rats in the water-deprived, compared with the water-replete, state. However, in the former condition, Brattleboro rats showed a profound and progressive hypotension in response to captopril, indicating an indispensable role for the renin-angiotensin system in the maintenance of blood pressure in these animals during water deprivation. 5. Only when the renin-angiotensin system and neural activity were inhibited did vasopressin express its full, independent, pressor potential in Long Evans rats. However, evidence was obtained that vasopressin may exert important effects on cardiovascular regulation via neural mechanisms and through interactions with the renin-angiotensin system.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Captopril; Ganglia; Male; Pentolinium Tartrate; Plasma Volume; Rats; Rats, Brattleboro; Renin-Angiotensin System; Vasopressins; Water Deprivation

The alpha adrenoceptor antagonists phenoxybenzamine and phentolamine are reported to have opposite effects on vasopressin release, the former inhibiting and the latter enhancing it. In this study we have assessed the functional involvement of vasopressin in the maintenance of blood pressure in conscious rats after administration of either phenoxybenzamine or phentolamine. In normal (Long-Evans) rats, phenoxybenzamine caused a small fall in arterial blood pressure, whereas phentolamine initially caused a profound hypotension which was followed by a fluctuating recovery back to normotensive levels. Similar effects were seen in rats deficient in hypothalamic vasopressin (Brattleboro strain). Administration of an antagonist of the cardiovascular actions of vasopressin [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-8-D-arginine vasopressin] in the presence of either alpha adrenoceptor antagonist alone was without effect in Long-Evans or Brattleboro rats, but, under these conditions, subsequent administration of captopril caused a profound and sustained hypotension in both strains. Administration of captopril in the presence of either alpha adrenoceptor antagonist alone caused a prompt fall in blood pressure which was sustained for the duration of the experiment in the Brattleboro rats. However, under these conditions, the blood pressure of the Long-Evans rats showed some recovery over the subsequent 45 min; this recovery was antagonized by [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-8-D-argine vasopressin]. It is concluded that after alpha adrenoceptor antagonism with either phenoxybenzamine or phentolamine, the renin-angiotensin system exerts a major pressor influence. However, after captopril administration in the presence of phenoxybenzamine or phentolamine, vasopressin contributes to the maintenance of arterial blood pressure in Long-Evans rats; the magnitude of this contribution is similar irrespective of the alpha adrenoceptor antagonist used.

Topics: Adrenergic alpha-Agonists; Animals; Arginine Vasopressin; Blood Pressure; Captopril; Drug Interactions; Heart Rate; Male; Phenoxybenzamine; Phentolamine; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins

Arterial blood pressures and heart rates were measured in water-replete and in water-deprived (48 h) conscious, adult rats that had received capsaicin (50 mg kg-1) or its vehicle neonatally. Resting arterial blood pressures and heart rates in capsaicin-treated rats were not different from the controls in either the water-replete or the water-deprived state. Inhibition of the vascular actions of vasopressin (with 1-beta-mercapto,-beta, beta-cyclopentamethylenepropionic acid, 8-D-arginine vasopressin, (d(CH2)5DAVP] had no significant effect on blood pressures in the water-replete animals but caused a significant hypotension in water-deprived rats; the magnitude of the hypotension was the same irrespective of whether the animals had received capsaicin or its vehicle. During angiotensin converting enzyme inhibition (with captopril) and ganglion blockade (with pentolinium), the vasopressin-mediated blood pressure recovery was more gradual in the capsaicin-treated animals than in the controls, but after 60 min blood pressures were similar in all groups. Collectively the results indicate that although the full development of vasopressin-dependent mechanisms following acute hypotension takes longer when a large proportion of unmyelinated afferent fibres have been destroyed by neonatal treatment with capsaicin, 48 h of water deprivation results in a normal involvement of vasopressin-dependent mechanisms in the maintenance of blood pressure.

Topics: Animals; Animals, Newborn; Arginine Vasopressin; Blood Pressure; Capsaicin; Captopril; Female; Heart Rate; Male; Pentolinium Tartrate; Rats; Rats, Inbred Strains; Renin-Angiotensin System; Vasopressins; Water Deprivation

Topics: Animals; Arginine Vasopressin; Blood Pressure; Desoxycorticosterone; Hypertension; Hypertension, Renovascular; Male; Rats; Rats, Inbred Strains; Sodium; Spinal Cord; Vasopressins

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.

Topics: 11-Hydroxycorticosteroids; Animals; Arginine Vasopressin; Blood Pressure; Cardiac Output; Dogs; Female; Heart Rate; Male; Renin; Vasopressins; Water Deprivation

In isolated rat hepatocytes, vasopressin evoked a large increase in the incorporation of [32P]Pi into phosphatidylinositol, accompanied by smaller increases in the incorporation of [1-14C]oleate and [U-14C]glycerol. Incorporation of these precursors into the other major phospholipids was unchanged during vasopressin treatment. Vasopressin also promoted phosphatidylinositol breakdown in hepatocytes. Half-maximum effects on phosphatidylinositol breakdown and on phosphatidylinositol labelling occurred at about 5 nM-vasopressin, a concentration at which approximately half of the hepatic vasopressin receptors are occupied but which is much greater than is needed to produce half-maximal activation of glycogen phosphorylase. Insulin did not change the incorporation of [32P]Pi into the phospholipids of hepatocytes and it had no effect on the response to vasopressin. Although the incorporation of [32P]Pi into hepatocyte lipids was decreased when cells were incubated in a Ca2+-free medium, vasopressin still provoked a substantial stimulation of phosphatidylinositol labelling under these conditions. Studies with the antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),8-arginine]vasopressin indicated that the hepatic vasopressin receptors that control phosphatidylinositol metabolism are similar to those that mediate the vasopressor response in vivo. When prelabelled hepatocytes were stimulated for 5 min and then subjected to subcellular fractionation. The decrease in [3H]phosphatidylinositol content in each cell fraction with approximately in proportion to its original phosphatidylinositol content. This may be a consequence of phosphatidylinositol breakdown at a single site, followed by rapid phosphatidylinositol exchange between membranes leading to re-establishment of an equilibrium distribution.

Topics: Animals; Arginine Vasopressin; Calcium; In Vitro Techniques; Insulin; Liver; Male; Phosphatidylinositols; Phospholipids; Rats; Stimulation, Chemical; Vasopressins