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PubMed1997

Vasopressin V2 receptor mRNA expression and cAMP accumulation in aging rat kidney.

The ability of the kidney to regulate water balance is impaired with age, although the secretion of vasopressin is maintained in senescent animals. This suggests that the cellular response to antidiuretic hormone is reduced in aging kidney. To test this hypothesis, the relationship between the expression of the vasopressin. V2 receptor mRNA and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- and 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old animals (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12, respectively). The concentration of vasopressin corresponding to half-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comparable sensitivity of the renal cells with age. The age-related impaired response to vasopressin of the V2 receptor was specific for females and was not observed in males. Direct stimulation of adenylyl cyclase by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V2 receptor mRNA level in the MTAL was constant between 10 and 30 mo whether the animals were normally hydrated or dehydrated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V2 mRNA or in posttranslational processing mechanisms or in the coupling between the V2 receptor and adenylyl cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Role of vasopressin in hypertension: studies using the Brattleboro rat.

Plasma arginine vasopressin (AVP) levels were elevated in both one-kidney, one-clip [1K-1C) and two-kidney, one-clip (2K-1C) hypertensive Long-Evans rats. Homozygous Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI), which are completely devoid of vasopressin, were made hypertensive using the 1K-1C Goldblatt models for renal hypertension. The 2K-1C DI rats developed hypertension at the same rate and to the same degree as normal 2K-1C hypertensive Long-Evans rats. The development of hypertension in 1K-1C DI rats was similar to the normal 1K-1C hypertensive Long-Evans rats. However, the absolute levels of systolic blood pressure reached were significantly less in the vasopressin-deficient rats. Treatment with 1-desamino-8-D-arginine vasopressin (DDAVP), the synthetic analogue of arginine vasopressin that has high antidiuretic but low pressor potencies, was associated with restoration of water balance in the volume-depleted DI rats and also restored blood pressure to hypertensive levels equivalent to the 1K-1C Long-Evans rats. These studies suggest that vasopressin is not essential for the development of experimental renal hypertension in rats but may contribute to the absolute levels of systolic blood pressure reached through its properties as an antidiuretic hormone.

Animals↗
PubMed1988

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.

Animals↗
PubMed1984

Stimulation of adrenocorticotropin/beta-endorphin release by synthetic ovine corticotropin-releasing factor in vitro. Enhancement by various vasopressin analogs.

Vasopressin analogs, which markedly differed in the ratio of pressor versus antidiuretic activity and also in ACTH/beta-endorphin-releasing activity, were used in the present study. The ability of vasopressin and these analogs to enhance the release of adrenocorticotropin-(ACTH-IR) and beta-endorphin-like immunoreactivity (beta-EI) induced by synthetic ovine corticotropin-releasing factor -CRF-(1-41)- was studied in vitro using incubated rat anterior pituitary quarters. Arginine vasopressin (AVP) potentiated the action of CRF-(1-41) 2- to 4-fold. Vasopressin analogs, which possess direct CRF-like activity when given alone, also enhanced beta-EI release caused by CRF-(1-41); the lowest concentration able to potentiate CRF-(1-41) activity was closely correlated with the ED50 value of these analogs for direct CRF-like activity. The vasopressin analog 1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-methyl)tyrosine-8-arginine-vasopressin blocked the release of ACTH-IR induced by AVP; however, this analog failed to prevent the potentiation by AVP of ACTH-IR release caused by CRF-(1-41), but enhanced itself the action of CRF-(1-41). Two analogs, which exhibited no direct CRF-like activity and which also did not antagonize the CRF-like activity of AVP, markedly enhanced the ACTH-IR and beta-EI response to CRF-(1-41).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1986

Secretion of vasopressin, oxytocin, and two neurophysins from rat hypothalamo-neurohypophyseal explants in organ culture.

Secretion of the neurohypophyseal principles arginine vasopressin, oxytocin, vasopressin-neurophysin, and oxytocin-neurophysin by hypothalamic-neurohypophyseal explants in organ culture was studied. The viability of explant cultures was tested on day 6 by their ability to incorporate 3H-amino acid into acid-precipitable protein, specifically vasopressin-neurophysin. The explants released all four neurosecretory products in a controlled manner during 8 successive days of culture. In addition, these substances were all present in neural lobes and hypothalami at the end of the culture period. Although the tissue retained a 1:1 molar ratio between the hormone and corresponding neurophysin, the levels of neurophysins in culture media were much higher than the levels of hormones. Through immunoprecipitation techniques we determined that both arginine vasopressin and oxytocin were unstable in culture media containing explants or in medium containing 10% heat-inactivated fetal calf serum. This suggests that neurophysins are more stable indicators of secretion by explants than are the corresponding hormones. An increased release of arginine vasopressin, oxytocin, vasopressin-neurophysin, and oxytocin-neurophysin occurred in response to elevated K+ and to increased sodium ions in the medium, and these four substances were released in different molecular proportions. The results indicate that explant cultures may be useful for comparisons of secretion of the two neurophysins and, to a more limited extent, of the two hormones in response to such stimuli.

Animals↗
PubMed1993

Enhancement of intracellular sodium by vasopressin in spontaneously hypertensive rats.

The arginine vasopressin-induced increase in intracellular sodium concentration was augmented in cultured rat vascular smooth muscle cells derived from 12-week-old spontaneously hypertensive rats (SHR) compared with those from 12-week-old normotensive Wistar-Kyoto (WKY) rats. This difference was enhanced by treatment with a Na+,K(+)-ATPase inhibitor, ouabain. The calcium-free state did not affect the basal intracellular sodium concentration but completely blocked the arginine vasopressin-induced increase in intracellular sodium concentration in both cell groups. The arginine vasopressin-mobilized cytosolic free calcium was enhanced in SHR compared with WKY rats. This enhancement was diminished but not completely inhibited in the calcium-free state. Also, arginine vasopressin-produced intracellular alkalinization was augmented in SHR. Pretreatment of both cell groups with a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, completely blocked arginine vasopressin-induced intracellular alkalinization and increased intracellular sodium concentration. Scatchard analysis showed that the V1 receptor number of either quiescent or proliferative cells of SHR was five to seven times greater than that of WKY rats, without any change in receptor affinity. These findings therefore indicate that the arginine vasopressin-induced increase in intracellular sodium concentration is augmented in vascular smooth muscle cells of SHR mediated through the enhancement of the mobilization of cytosolic free calcium and the activity of sodium-hydrogen exchange, which depends on an increase in V1 receptor number.

Animals↗
PubMed1998

Arginine vasopressin-mediated stimulation of nitric oxide within the rat renal medulla.

The present study was designed to determine whether arginine vasopressin (AVP) can stimulate nitric oxide (NO) production within the renal medulla and thereby modulate renal medullary blood flow. An in vivo microdialysis/NO trapping technique was used to determine changes in medullary interstitial [NO]. AVP (2 ng/kg per minute) was delivered into the renal medullary interstitium and resulted in a significant increase in renal medullary [NO] of 35%, which was blocked by pretreatment with nitro-L-arginine methyl ester (L-NAME) (1.3 microg/kg per minute) administered into the renal medullary interstitium. The vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) resulted in a significant increase of 32% in renal medullary interstitial [NO]. No change in renal medullary interstitial [NO] was observed after selective vasopressin V1 receptor stimulation. Laser-Doppler flowmetry with implanted optical fibers was performed to measure cortical and medullary blood flow changes within the kidney. Renal interstitial infusion of dDAVP in rats pretreated with a vasopressin V1 receptor antagonist resulted in a 15% increase (P<0.05) in medullary blood flow, which was completely blocked by pretreatment with L-NAME (1.3 microg/kg per minute). This study demonstrates that AVP increases renal medullary interstitial [NO] through vasopressin V2 receptor stimulation, which in turn elevates blood flow to the renal medulla.

Animals↗
PubMedDate not supplied

Interaction of the sympathetic nervous system with vasopressin and renin in the maintenance of blood pressure.

To evaluate the partial contributions and interaction of three vasopressor systems in blood pressure maintenance, nephrectomized rats and rats with intact kidneys were submitted sequentially to catecholamine depletion, elimination of vasopressin's vasoconstrictor action, and (for those with kidneys in situ) angiotensin blockade. Catecholamine depletion decreased blood pressure and stimulated vasopressin levels in all rats, but significantly more so in the anephric ones. Subsequent injection of an antagonist to the vasopressor effect of vasopressin produced a lasting fall of blood pressure in anephric rats, but only transient fall in those with intact kidneys. Infusion of teprotide--an angiotensin converting enzyme inhibitor--in the latter animals also produced transient blood pressure fall, but if this were followed by injection of the vasopressin antagonist, the pressure remained low for several hours. Blood pressure levels were closely correlated with those of plasma catecholamines throughout these maneuvers. Catecholamine levels were inversely correlated with those of plasma vasopressin, which were far greater in anephric rats through both stimulation and accumulation. Plasma renin activity was increasingly stimulated by falling blood pressure after each maneuver in rats with intact kidneys. Thus, it appears that in the resting state the sympathetic nervous system is more involved in the maintenance of blood pressure, whereas vasopressin and renin are important backup mechanisms.

Animals↗
PubMed1990

Sexual dimorphism in vasopressin and cardiovascular response to hemorrhage in the rat.

There is evidence for sex-related differences in the cardiovascular actions of vasopressin. Furthermore, receptors for the gonadal steroid hormones are located in centers in the brain involved in the control of vasopressin release and in cardiovascular regulation. We have, therefore, examined the effects of hemorrhage on mean arterial blood pressure, the plasma vasopressin concentration, and plasma renin concentration in conscious male and female rats. In preliminary experiments, no differences were found in blood and plasma volumes with respect to either sex or phase of the estrous cycle. In separate experiments, rats were subjected to two hemorrhages of 10% of blood volume, separated by an interval of 15 minutes. There were no substantial gender- or cycle-related differences in the ability of hemorrhaged rats to maintain mean arterial blood pressure or increase plasma renin concentration. The increase in plasma vasopressin concentration was greater in proestrous females than in males after the first hemorrhage and in diestrous, proestrous, and metestrous females than in males after the second hemorrhage. Pretreatment with a V1-receptor antagonist was without statistically significant effect on the mean arterial blood pressure responses in males, but it impaired blood pressure compensation in females. There are, then, gender- and cycle-related differences in vasopressin responses to hemorrhage, and vasopressin appears particularly important for blood pressure compensation to hemorrhage in female rats.

Animals↗
PubMed1981

125I-8-L-arginine vasopressin binding to human mononuclear phagocytes.

The binding of vasopressin to human circulating blood cells was examined. Direct binding studies with preparations of single cell types indicated that the mononuclear phagocyte system is almost entirely responsible for binding of the hormone. Binding of 125I-8-L-arginine vasopressin (AVP) (40 pM) in the presence of excess unlabeled hormone was saturable (2.8 +/- 0.4 fmol/2 x 10(6) cells per ml), was linear with cell number, was dependent upon the concentration of the radioligand used, and was reversible. Binding equilibrium was achieved in 30--40 min at 22 degrees C. Scatchard analysis of binding at this time showed an apparent dissociation constant of 25 +/- 0.21 pM, providing an estimate of 640 +/- 80 sites/cell. Pretreatment of the cells with cytochalasin B, an agent that can block phagocytosis, did not modify radioligand binding, which indicates that 125I-AVP uptake by the cells is due to binding and not to endocytosis. Specificity of vasopressin-sensitive sites on mononuclear phagocytes was demonstrated with a series of vasopressin analogues with various degrees of antidiuretic potency, and with peptide hormones that bind to specific receptors on circulating blood cells but that lack antidiuretic activity. AVP (40 pM) elevated the intracellular level of cyclic AMP from 137 +/- 8.6 to 350 +/- 20.5 pmol/mg cell protein. The binding affinities of the various analogues were correlated with their ability to stimulate intracellular cyclic AMP synthesis (Lys8-vasopressin less than deamino(8-D-Arg)-vasopressin less than oxytocin).

Arginine Vasopressin↗
PubMed1977

Arginine vasopressin secretion in thyroidectomized sheep..

Indwelling, exteriorized, jugular vein catheters were placed in five thyroidectomized ewes at a time when myxedema was manifested clinically and chemically and three euthyroid sheep were used as controls. Post-operatively, tracer doses of [125I]-iodovasopressin were injected and serial blood specimens were obtained for determination of volume of distribution, plasma disappearance, and blood production rates. Serum vasopressin was measured by radioimmunoassay. The mean volumes of distribution for vasopressin in the hypothyroid and euthyroid sheep, respectively, were 8.15 and 5.90 liters, mean t1/2 of vasopressin 9.5 and 19.3 min, mean serum vasopressin concentrations 5.1 and 1.2 muU/ml, and mean blood production rates 2.84 and 0.23 mU/kg/h. Renal and organ biologic effectiveness of the elevated vasopressin levels was suggested by the lowered serum osmolalities in the hypothyroid sheep over controls (272 vs. 301 mosmol/kg). These results suggest an augmented secretion of vasopressin in the myxedematous state.

Animals↗
PubMed1976

Studies on the corticotrophin-releasing activity of vasopressin, using ACTH secretion by cultured rat adenohypophyseal cells.

CRF activity of synthetic vasopressins and pitressin was studied in an in vitro system of cultured rat adenohypophyseal cells using direct measurement of ACTH by radioimmunoassay. Pitressin (posterior pituitary extract) induced a dose-related secretion of ACTH whereas synthetic arginine or lysine vasopressin were devoid of CRF activity, even with the largest tested dose (4 mug/ml). No potentiation of the CRF activity of hypothalamic extract was observed with any vasopressin preparation studied. We concluded that: 1) the CRF activity of posterior pituitary extract is not due to vasopressin, and 2) the ACTH secretion induced by vasopressin administration in vivo is unlikely to be due to a direct effect of vasopressin on adenohypophyseal cells.

Adrenocorticotropic Hormone↗
PubMed1984

Vasopressin as a possible contributor to hypertension.

The role of vasopressin as a pressor agent to the hypertensive process was examined. Vasopressin plays a major role in the pathogenesis of DOCA-salt hypertension, since the elevation of blood pressure was not substantial in the rats with lithium-treated diabetes insipidus after DOCA-salt treatment. Administration of DDAVP which has antidiuretic action but minimal vasopressor effect failed to increase blood pressure to the levels observed after administration of AVP. Furthermore, the pressor action of vasopressin appears to be important in the development of this model of hypertension, since the enhanced pressor responsiveness to the hormone was observed in the initial stage of hypertension. Increased secretion of vasopressin from neurohypophysis also promotes the function of the hormone as a pathogenetic factor in hypertension. An unproportional release of vasopressin compared to plasma osmolality may be induced by the absence of an adjusting control of angiotensin II forming and receptor binding capacity for sodium balance in the brain. However, the role of vasopressin remains to be determined in human essential hypertension.

Animals↗
PubMed2004

Involvement of endogenous vasopressin in high plasma osmolality-induced anorexia via V1 receptor-mediated mechanism.

It is known that water deprivation or injection of hypertonic saline induces anorexia. The present study examined the possible involvement of vasopressin in the suppression of food intake during high plasma osmolality. Intraperitoneal injection of vasopressin (20 microg/kg) into male rats significantly suppressed food intake for 1 hr. This anorectic effect of vasopressin was reversed by simultaneous injection of a peptide antagonist for V(1) receptor (40 microg/kg), but not for V(2) receptor (40 microg/kg). Intraperitoneal injection of hypertonic saline (20% NaCl, 2 ml/kg) similarly suppressed food intake for 2 hr, which was associated with a transient increase in plasma vasopressin concentrations. This hypertonic saline-induced suppression of food intake was blocked by a V(1) receptor antagonist. Vasopressin (40 ng/2 microl) directly administered into the third ventricle of the brain also suppressed food intake for 1 hr. These results suggest that vasopressin participates in the suppression of food intake during high plasma osmolality, the action of which is mediated by V(1) receptors in the brain.

Analysis of Variance↗
PubMed2006

Evolving role of vasopressin in the treatment of cardiac arrest.

Sudden cardiac arrest is a major public heath problem, affecting more than 450,000 individuals annually. Response time and the initiation of cardiopulmonary resuscitation (CPR) remain the most important factors determining successful revival. During resuscitation, sympathomimetics are given to enhance cerebral and coronary perfusion pressures in an attempt to achieve restoration of spontaneous circulation. Epinephrine has been the preferred vasopressor since the inception of advanced cardiac life support, although the lack of definitive evidence regarding its effectiveness has created much controversy surrounding its use, including the optimum dosage. Vasopressin is an alternative vasopressor that, when given at high doses, causes vasoconstriction by directly stimulating smooth muscle V1 receptors. The 2000 American Heart Association (AHA) guidelines commented that vasopressin is a reasonable first-line vasopressor in patients with ventricular fibrillation or pulseless ventricular tachycardia. Since release of those guidelines, additional human studies support an expanded role for vasopressin, whereas other studies cast doubt regarding its efficacy compared with epinephrine. The AHA recently released revised guidelines for CPR and emergency cardiovascular care. The consensus was that vasopressors should remain a part of pulseless sudden cardiac arrest management, with epinephrine 1 mg every 3-5 minutes being the recommended adrenergic of choice. In these revised guidelines, the role of vasopressin expanded beyond previous recommendations, despite the recommendation being downgraded to class indeterminate. The guidelines comment that one dose of vasopressin 40 U may replace the first or second dose of epinephrine in all pulseless sudden cardiac arrest scenarios, including asystole and pulseless electrical activity. A consistent theme with all vasopressors in sudden cardiac arrest is that additional studies are necessary to clearly document greater efficacy compared with no treatment. Further evaluation is warranted to better assess the role of vasopressin in asystolic sudden cardiac arrest, as well as its use with epinephrine, and to determine its optimal timing of administration and potential synergistic effects.

Arginine Vasopressin↗
PubMed1987

Renal vasopressin receptors in ageing C57BL/Icrfat mice.

The mechanism of water conservation is impaired in ageing mammals. An age-related defect in the release of vasopressin has been implicated but, more recently, attention has moved to the renal component of the water conservation mechanism. Previous studies using renal cells prepared from mice of different ages have shown that the threshold dose of vasopressin required to elicit a significant rise in cyclic AMP (cAMP) was greater in older animals. The dose-response curve was moved to the right in 35-month-old mice, i.e. the concentration of vasopressin required to give maximum cAMP output was increased. To investigate this further we examined the binding of vasopressin to renal medullary cells maintained in short-term culture, to determine whether the decreased response of cAMP levels to vasopressin is due to changes in hormone-receptor interaction. In 6-month-old male mice the dissociation constant (Kd) was 2.38 nmol/l and the maximum binding of the hormone (Bmax) was 47.6 fmol/10(6) cells, and at 30 months of age Kd was 2.37 nmol/l and Bmax was 47.0 fmol/10(6) cells. In female mice the changes were more complicated because the data for the 6-month-old mice could be split into two groups. It is concluded that there are no age-related differences in the numbers of receptors or their affinity for vasopressin, and that the decreased cAMP response is probably associated with post-receptor mechanisms in this species.

Aging↗
PubMed1994

Effects of exogenous relaxin on oxytocin and vasopressin release and the intramammary pressure response to central hyperosmotic challenge.

Experiments were done to study the effects of porcine relaxin on osmotically evoked changes in intramammary pressure and the release of oxytocin and vasopressin in anaesthetized rats. Injections (1 microliter) of hypertonic (0.75 M) NaCl into the left lateral cerebral ventricle were used to induce consistent rises in intramammary pressure and the release of oxytocin and vasopressin. Plasma hormone concentration was determined by radioimmunoassay. Relaxin (5 micrograms i.v.) significantly (P < 0.05) suppressed the intramammary pressure response to osmotic challenge 5 and 10 min after treatment. However, pretreatment with a specific vasopressin V1 receptor antagonist completely negated the effect of relaxin on intramammary pressure. Baseline levels of oxytocin and vasopressin in unstimulated rats were 41 +/- 1.6 and 36 +/- 1.1 pmol/l respectively. Osmotic challenge induced significant (P < 0.05) rises in plasma levels of both hormones (62.8 +/- 1.1 and 67.9 +/- 1.2 pmol/l respectively) which were further augmented by relaxin (81.3 +/- 1.8 and 117.1 +/- 2.4 pmol/l respectively; P < 0.05). The data confirm that central osmotic challenge provokes the release of oxytocin and vasopressin but the effects of oxytocin at the level of the mammary gland may be obscured by the action of vasopressin affecting blood flow to the gland.

Animals↗
PubMed2001

Increased abundance of distal sodium transporters in rat kidney during vasopressin escape.

Hyponatremia is associated with inappropriately elevated vasopressin levels. A brisk natriuresis precedes the escape from this antidiuresis. Thus, the hypothesis was that the abundance of one or more of the sodium transporters of the distal tubule (a site for fine tuning of sodium balance) would be altered during vasopressin escape. Semiquantitative immunoblotting was used to examine the regulation of abundance of several sodium transporters/channels of the thick ascending limb through the collecting duct in the rat model. Osmotic minipumps to infuse dDAVP, the V2-selective vasopressin agonist (5 ng/h) for the entire experiment, were implanted in Male Sprague-Dawley rats. After 4 d, rats were divided into a control (dry AIN-76 diet/ad libitum water) or a water-loaded (gelled-agar-AIN-76 diet/ad libitum water) group. Rats were killed after 1, 2, 3, or 7 additional days. The water-loaded rats were hyponatremic (plasma Na+, 98 to 122 mmol/L) and manifested the expected early natriuresis and diuresis of vasopressin escape. Water loading (with dDAVP infusion) resulted in increased whole-kidney abundances of the thiazide-sensitive Na-Cl co-transporter, the alpha-subunit of the epithelial sodium channel (ENaC), and the 70-kD dimer of the gamma-subunit of ENaC. No changes were observed for the ss-subunit of ENaC. Similar protein changes have recently been associated with elevated aldosterone levels in rats. However, plasma aldosterone levels were significantly suppressed in this model. These data suggest that several distal sodium reabsorptive mechanisms are upregulated during vasopressin escape; this may help to attenuate the developing hyponatremia resulting from water loading when vasopressin levels are inappropriately elevated.

Aldosterone↗