Arginine Vasopressin Antiserum Research Articles

Oxytocin, but not arginine vasopressin is involving in the antinociceptive role of hypothalamic supraoptic nucleus

Our pervious study has demonstrated that the hypothalamic supraoptic nucleus (SON) plays a role in pain modulation. Oxytocin (OXT) and arginine vasopressin (AVP) are the important hormones synthesized and secreted by the SON. The experiment was designed to investigate which hormone was relating with the antinociceptive role of the SON in the rat. The results showed that (1) microinjection of l-glutamate sodium into the SON increased OXT and AVP concentrations in the SON perfusion liquid, (2) pain stimulation induces OXT, but not AVP release in the SON, and (3) intraventricular injection (pre-treatment) with OXT antiserum could inhibit the pain threshold increase induced by SON injection of l-glutamate sodium, but administration of AVP antiserum did not influence the antinociceptive role of SON stimulation. The data suggested that the antinociceptive role of the SON relates to OXT rather than AVP.

Involvement of Vasopressin in Histamine- and Stress-Induced Prolactin Release: Permissive, Mediating or Potentiating Role?

Arginine vasopressin (AVP) appears to be involved in the histamine (HA)- and stress-induced prolactin (PRL) release. The present investigation was performed in male rats to clarify whether the role of AVP in HA- and restraint stress-induced secretion of PRL is mediating (i.e., the effect of HA or stress is transmitted via AVP) or permissive (i.e., the presence of AVP is required to obtain a stimulatory effect of HA or stress on PRL secretion). Furthermore, we studied whether AVP possessed a potentiating effect on the HA- or stress-induced PRL release. PRL secretion was stimulated 14- to 17-fold by intracerebroventricular infusion of HA (270 nmol) or by 5 min of restraint stress. These effects were inhibited about 80% by immunoneutralization of endogenous AVP with a specific AVP antiserum (abAVP). When specific AVP V1- or V2-receptor agonists, which were not bound by the AVP antiserum, were administered intravenously together with the AVP antiserum, the PRL response to HA or restraint stress was partly (> 50%) reestablished. This effect was observed at low (1.2 or 0.1 nmol) as well as high (3.8 or 0.4 nmol) doses of agonists and when these were administered alone or in combination. In non-immunoneutralized animals, separate administration of agonists at low or high doses as well as combined administration of agonists at low doses had no or only a minor effect on PRL secretion, while combined administration of V1- and V2-agonist in high doses stimulated PRL secretion 6-fold. Taken together, these observations indicate that AVP has a permissive role.(ABSTRACT TRUNCATED AT 250 WORDS)

Permissive, mediating and potentiating effects of vasopressin in the ACTH and beta-endorphin response to histamine and restraint stress.

We investigated in conscious, male rats (1) whether the role of arginine-vasopressin (AVP) in histamine (HA)- and/or restraint stress-induced stimulation of ACTH and beta-endorphin (beta-END) secretion is mediating and/or permissive and (2) whether AVP possesses a potentiating effect on HA- or stress-induced release of ACTH and beta-END. Administration of a specific V1 receptor agonist stimulated ACTH and beta-END secretion dose-dependently while a V2 receptor agonist had no stimulating effect. ACTH and beta-END secretion was stimulated 2- to 3-fold by intracerebroventricular (i.c.v.) infusion of HA (270 nmol) or by 5 min of restraint stress. These effects were inhibited approximately 80% by immunoneutralization of endogenous AVP using a specific AVP antiserum. When the 'AVP tone' was restored in immunoneutralized animals by administration of the specific AVP V1 receptor agonist, which was not bound by the AVP antiserum and had no ACTH and beta-END-releasing effect in the dose used, the ACTH and beta-END response to HA or restraint stress was almost completely reestablished. The specific AVP V2 receptor agonist, which was not bound by the AVP antiserum, reestablished only in part the response of ACTH and beta-END to HA or restraint stress in immunoneutralized animals. AVP administered in doses which had no or minimal ACTH or beta-END releasing effect in itself enhanced the ACTH or beta-END response to submaximal stimulation with HA or restraint stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of endotoxin fever and release of arginine vasopressin by dehydration in the guinea pig.

Arginine vasopressin (AVP), synthesized in hypothalamic neurons, is transported in axons either to the pituitary for release into the circulation or to different brain areas. In our previous experiments we documented central antipyretic AVP pathways from the hypothalamus to the ventrolateral septal area in the limbic system. In the present study we investigated if osmotic stimulation is able to activate peripheral and central release of AVP concurrently and if the antipyretic pathways are influenced by this kind of stimulation. In dehydrated animals (24 h water deprivation) the arterial blood plasma level of AVP doubled causing antidiuretic effects. Also the concentration of AVP in push-pull perfusates of the limbic septal area was significantly higher in dehydrated (5.6 pg AVP/ml perfusate) than in control animals (2.6 pg AVP/ml perfusate). The febrile response to bacterial endotoxin was reduced by 50% in dehydrated guinea pigs compared to controls, statistically significant between 30 and 180 min after pyrogen application. A microinfusion of AVP antiserum into the limbic septal area enhanced the fever reaction of dehydrated guinea pigs compared to the effects of a microinfused preimmune serum, in this case statistically significant between 180 and 360 min after application. From these data we assume a simultaneous activation of peripheral and central release of AVP with antidiuretic and antipyretic effects by dehydration.

Mediation of the Stress-Induced Prolactin Release by Hypothalamic Histaminergic Neurons and the Possible Involvement of Vasopressin in This Response*

We investigated the role of histamine (HA) in the neuroendocrine regulation of PRL secretion in conscious male rats. Blood samples were obtained by decapitation of the animals at 0 min. Intracerebroventricular infusion of HA (34-540 nmol at -15 min) stimulated PRL secretion dose dependently with an ED50 of approximately 135 nmol. Inhibition of neuronal HA synthesis by the specific histidine decarboxylase-inhibitor (S)alpha-fluoro-methylhistidine (alpha FMH; 100 mumol/kg ip at -6 h or 400 mumol/kg ip at -20 h and -6 h) caused a 50% reduction (P less than 0.01) in the PRL response to 5 min of restraint stress. Inhibition of neuronal HA metabolism by the specific histamine-methyltransferase-inhibitor SKF-91488 (400 and 800 nmol icv at -20 min) augmented the restraint stress-induced PRL release 26% and 37%, respectively (P less than 0.05). The two enzyme inhibitors had no or only modest effect on the basal PRL secretion. Pretreatment with a specific antiserum (0.5 ml) to arginine vasopressin (AVP) or an AVP antagonist (25 nmol) administered iv at -20 min inhibited the PRL response to HA (270 nmol icv) 80% and 45%, respectively (P less than 0.01) and inhibited the PRL response to restraint stress 70% (P less than 0.01). In contrast, pretreatment with a specific oxytocin (OT) antagonist (50 nmol) had no effect on the HA- or stress-induced PRL release. The AVP antiserum showed less than 0.0003% cross-reactivity with OT, and radiolabeled OT did not bind to serial dilutions of plasma from rats treated with the AVP antiserum. The AVP antiserum or the AVP antagonist almost prevented the PRL release induced by iv infusion of 800 pmol AVP or a posterior pituitary extract. Infusion of AVP (24-800 pmol iv at -15 min) stimulated PRL secretion dose dependently. However, the dose of AVP (800 pmol) required to induce an increase in plasma PRL similar to that obtained by HA-stimulation, led to a rise in plasma AVP which was approximately 1000-fold higher than that induced by HA, which increased plasma AVP 2-fold. Restraint stress had no effect on the plasma AVP level. We conclude that neuronal HA participates in the mediation of the PRL response to stress and that the stress- and HA-induced release of PRL may involve AVP, whereas an involvement of OT seems unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)

Thermoadaptive influence on reactivity pattern of vasopressinergic neurons in the guinea pig.

In cold-adapted guinea pigs, increased amounts of arginine-vasopressin (AVP) immunoreactive material could be visualized in neurons of the supraoptic and paraventricular nucleus, in fibers projecting to the neurohypophysis and in fiber terminals in the ventral lateral septum and in the amygdala. In warm-adapted animals the reactivity to AVP antiserum was poor in all neuronal structures examined. High AVP-immunoreactivity was accompanied by a reduced febrile response to bacterial pyrogen in cold-adapted guinea pigs.

Sodium salicylate: alternate mechanism of central antipyretic action in the rat.

Infusion of sodium salicylate (50.0 or 100.0 micrograms/microliters) into the ventral septal area (VSA) of the rat brain suppressed Prostaglandin-E1-induced hyperthermia. Infusion of artificial cerebrospinal fluid (aCSF) or 10.0 micrograms doses of salicylate did not. The suppression of intracerebroventricularly-induced (icv) Prostaglandin E1 (PGE1) hyperthermia was not due to a hypothermic action of salicylate since salicylate infusions given during cold exposure (10.0 degrees C) did not lower core body temperatures. A possible interaction between salicylate and endogenous arginine vasopressin (AVP) was investigated. Infusion of both salicylate (50.0 micrograms/microliters) and either AVP antiserum or AVP antagonist into the VSA resulted in PGE hyperthermias occurring at levels which were not different from control levels as opposed to enhanced hyperthermia (antiserum or antagonist alone) or suppressed hyperthermia (salicylate alone). These results are consistent with the notion that sodium salicylate infusions within the VSA enhance AVP action and thus bring about the attenuation of PGE-induced hyperthermia.

Single-Dose Ethanol Administration Activates the Hypothalamic-Pituitary-Adrenal Axis: Exploration of the Mechanism of Action

Activation of the hypothalamic-pituitary-adrenal axis (HPAA) by single-dose ethanol administration, which achieved moderately high blood ethanol levels, was explored in naive rats in order to determine the mechanism of ethanol's activation of the stress axis. Adult male rats received a single dose (3.2 g/kg body weight-1 of a 12% solution of ethanol in physiological saline. The plasma concentration of immunoreactive (ir) adrenocorticotropic hormone (ACTH), beta-endorphin (BE) and corticosterone (CS) was determined by radioimmunoassay, whereas, plasma concentrations of epinephrine (E) and norepinephrine (NE) were quantified following reverse-phase liquid chromatographic separation and amperometric detection. Ethanol induced maximal plasma ACTH levels within minutes, which declined toward basal levels by 60 min, whereas, plasma concentration of CS rose rapidly and remained elevated at 60 min. Plasma ACTH and CS levels in saline-treated control animals did not vary significantly at any time point. Consistent with co-release of ACTH from corticotrophs, the plasma concentration of ir-BE increased 5-fold at 15 min and declined towards basal levels at 60 min after-ethanol challenge. Plasma E increased 10- to 20-fold as compared to saline controls or preinjection levels and returned to preinjection levels by 90 min, in a manner similar to ethanol-induced changes in proopiomelanocortin-derived peptides and CS. Removal of the adrenal medulla and thus the source of E prior to ethanol administration, did not attenuate activation of the HPAA. Passive immunoneutralization of arginine vasopressin (AVP), using a high-titer AVP antiserum and a protocol which was found to block ether-induced ACTH secretion by 40% in adult male rats, failed to even partially block ethanol-induced ACTH or CS secretion. The results of this study indicate that neither adrenal medulla-derived E nor AVP are significant regulators or coregulators of corticotroph secretions following a moderately high, single-dose, intragastric administration of ethanol.

Mechanism of pressor effects of angiotensin II microinjected into the fourth ventricle of rabbits.

The experiments were performed on 53 anesthetized, paralyzed and ventilated rabbits. 1) Microinjectjon of 5 μg angiotensin II (A II) into the fourth ventricle elicited increase of mean arterial pressure and renal nerve discharges, but decrease of heart rate. When the baroreceptor reflex was eliminated before microinjection, the decrease of heart rate no longer occurred. 2) Pretreatment with 1 μg prazosin decreased the pressor effect of A II and eliminated the increase of renal nerve discharges, whereas 3 μg yohimbine produced no effect on the pressor response of A II. 3) Pretreatment with 1 μg prazosin and 10 μ1 arginine-vasopressin antiserum together could abolish the pressor effect of A II. The experimental results suggest that microinjection of A II into the fourth ventricle had central pressor effect, which might be mediated through central α1-adrenoceptor and central vasopressin.

Presence of pro-vasopressin mRNA, neurophysin and arginine vasopressin in mouse anterior pituitary cells and the AtT-20 corticotrophic tumour cell line.

Pro-vasopressin mRNA, neurophysin and arginine vasopressin (AVP) were assayed in the mouse anterior pituitary gland, in mouse anterior pituitary cells in culture and in the AtT-20 corticotrophic tumour cell line. Northern blot analysis revealed the presence of an approximately 700 base pair pro-vasopressin mRNA in anterior pituitary and AtT-20 cells. Neurophysin, identified by immunoblots, and AVP, identified by high-performance liquid chromatography and cross-reactivity with AVP antiserum, were detected in anterior pituitary cells and AtT-20 cells. Immunocytochemical staining with anti-neurophysin showed that approximately 40-45% of the dissociated anterior pituitary cells in culture and greater than 95% of the AtT-20 cells were stained. Anterior pituitary cells in culture and AtT-20 cells had a basal level of release of AVP in the 0.01-0.1 nM range. These results indicate that anterior pituitary cells and AtT-20 cells have the ability to synthesize and process pro-vasopressin to AVP and neurophysin, endogenously.

Effects of intracerebroventricular microinjection of angiotensin III on the cardiovascular activities in rabbits.

In mongrel rabbits intracerebroventricular microinjected angiotensin III (A III, 4 nmol) and angiotensin II (A II 4 nmol) equally evoked increase of mean arterial pressure and decrease of heart rate respectively. However, intracerebroventricular preinjection of saralasin, prazosin or arginine-vasopressin antiserum or intravenous preinjection of phentolamine could markedly attenuate the above cardiovascular effects of A III and A II respectively. The results indicated that the response intensity and mechanism of the central presser effect of A III were similar to those of A II.

The role of vasopressin in acute cerebral vasospasm. Effect on spasm of a vasopressin antagonist or vasopressin antiserum.

An experimental model of subarachnoid hemorrhage (SAH) in the Sprague-Dawley rat induces angiographically demonstrable, reproducible biphasic vasospasm of the vertebrobasilar system. The acute vasospasm is maximum at 10 minutes and the maximum late vasospasm occurs 2 days after the SAH. Brattleboro rats, which are deficient in arginine vasopressin (AVP), do not have acute vasospasm after SAH but exhibit a degree of late vasospasm that is not significantly different from that seen in Sprague-Dawley rats. Cisternal injection of AVP induced acute vasospasm in Sprague-Dawley rats with a duration similar to that seen after cisternal blood injection; however, at 2 days, the vessel diameter was normal. Intravenous AVP antagonist or intracisternal AVP antiserum administered prior to the SAH prevented the development of acute vasospasm without affecting the late phase. The data suggest that an increased release of AVP in the cerebrospinal fluid is involved in the development of acute cerebral vasospasm.

Neonatal administration of vasopressin antiserum induces long-term deficits on active and passive avoidance behaviour in rats

Two-day-old male rats received a subcutaneous injection of arginine-vasopressin (AVP) antiserum and avoidance behaviour was studied 3 months later. Rats treated with the antiserum showed a clear retention deficit in a one-trial learning, step-through passive avoidance situation. Anti-AVP treatment also induced an impairment on the acquisition of a two-way active avoidance task. Systolic blood pressure was lower than normal in these animals. The results obtained appear to be indicative of the high vulnerability of the developing nervous system, and are discussed in the context of the different hypothesis on the role of central or peripheral mechanisms in the behavioural effects of AVP. Although no definite conclusions may be drawn in this regard, the present data strongly suggest that neonatal administration of AVP antiserum exerts long-lasting effects upon the functionality of several physiological mechanisms related to the behavioural adaptation of the organism.

Preparation of 125I-labelled arginine vasopressin for radioimmunoassay

Despite the common use of gel chromatography for separation of products from radioiodination of arginine vasopressin, reported specific activities of the material used as radioimmunoassay label cover a very wide range. We present evidence that, while the choice of iodination reducing agent is critical in the case of arginine vasopressin, the volume of the gel bed is almost certainly the major reason for this discordance. On a suitably large column essentially carrier-free mono and diiodinated arginine vasopressin are readily separated from other iodination products, and when the arginine vasopressin antiserum is primarily directed toward the three amino acid tail of the molecule, the diiodinated label can be successfully employed in a radioimmunoassay. This observation is of particular significance in arginine vasopressin radioimmunoassay, where a detection limit < 1 fmol is required to distinguish subnormal from normal plasma concentrations.

Functional relations of crab molt-inhibiting hormone and neurohypophysial peptides

Biological and immunological relationships between molt-inhibiting hormone (MIH) activity in eyestalk ganglia extracts of the crab, Cancer antennarius Stimpson, and peptides of the vasopressin-oxytocin family were assessed. Lysine vasopressin (LVP), arginine vasopressin (AVP), vasotocin (VT), and oxytocin (OT) mimicked MIH action by inhibiting ecdysteroid production of Y-organ segments in vitro with the relative potencies LVP>AVP>VT>>>OT. The inhibitory effect was reversible and specific (6 other peptides did not alter Y-organ activity). MIH and LVP increased Y-organ cyclic adenosine 3′,5′ monophosphate (cAMP) levels dose-dependently and with identical time course in which the rise in cAMP preceded inhibition of ecdysteroid production. The synthetic vasopressin antidiuretic agonist 1-deamino-8-D-AVP (dDAVP) inhibited Y-organ steroidogenesis dose-dependently; the vasopressin analog ([1(B-mercapto-β,β-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine[AVP) (d(CH 2) 5Tyr(Me)AVP), a vasopressor antagonist, had no effect on basal or MIH-suppressed steroidogensis. AVP antiserum abolished the inhibitory action of MIH, LVP, and AVP. Competitive binding curves for MIH, LVP, AVP, VT, and OT with the AVP antiserum suggested that MIH is most closely related to LVP. MIH may be structurally related to the vasopressins and act on Y-organ cells via type V2 (cAMP-linked) receptors.

Role of arginine vasopressin in control of ACTH and LH release during stress

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 μl injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occured in doses ranging from 10 ng (10 p mole)-10 μg/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.

Fate of vasopressin perfused into nephrons of Wistar and Brattleboro (diabetes insipidus) rats.

1. Iodinated vasopressin was microinjected into early proximal or distal tubules or Wistar and Brattleboro (diabetes insipidus) rats. Sites of infusion were determined by the lissamine green transit time method. 2. Urinary recovery of 125I after proximal and distal injections was 89 +/- SE 1.7% and 94 +/- 1.0% in Wistar rats (corrected for inulin) and 81 +/- 2.0 and 92 +/- 2.0% in Brattleboro rats (uncorrected); injection of hormone into vascular stars resulted in similar 125I recoveries from punctured and contralateral kidneys. 3. Radioactive substances excreted after perfusing proximal and distal sites in Brattleboro animals, and 125I-labelled hormone added to urine from the contralateral kidney, bound similarly to a specific arginine vasopressin antiserum and demonstrated similar radioactive elution profiles after passage through Sephadex G25 columns. 4. Incubation of labelled and unlabelled vasopressin with rat kidney homogenates resulted in similar and complete degradation of the hormone. 5. Results indicate that most of the vasopressin injected into either proximal or distal nephrons enters the urine intact, and no evidence of tubular secretion was found when perfusing vascular stars. Enzymes in rat renal tissue degrade labelled vasopressin, but the ability of the proximal tubule to hydrolyse the 125I-labelled vasopressin is limited, especially when compared with that reported for several linear peptide hormones.

Studies on the role of vasopressin in blood pressure control of spontaneously hypertensive rats with established hypertension (SHR, stroke-prone strain).

We investigated the role of arginine-vasopressin (AVP) in maintaining the blood pressure of spontaneously hypertensive (SH) rats (stroke-prone strain) with established hypertension (22--28 weeks of age). In comparison with normotensive Wistar Kyoto (WKY) rats, plasma AVP concentrations of SH rats with benign hypertension (BH) were elevated twofold and in rats with severe or malignant hypertension (S-MH), fourfold. The height of the blood pressure was quantitatively related to plasma AVP in both BH and S-MH rats, the overall correlation coefficient being 0.66 (p less than 0.001). The intravenous injection of a specific AVP antiserum into conscious and unrestrained rats lowered blood pressure in 4 BH rats by 48 +/- 14 mm Hg and in 4 S-MH rats by 78 +/- 10 mm Hg and had only a marginal effect in 4 normotensive WKY rats. Infusion of saralasin did not lower blood pressure in WKY and BH rats and reduced blood pressure in only 2 of 7 S-MH rats tetsted (by 15 and 20 mm Hg). During AVP infusion the blood pressure of SH rats increased more (p less than 0.001) and heart rate fell much less (p less than 0.001) than in WKY rats. It is concluded that in SH rats with established hypertension, plasma AVP plays an important role in the maintenance of high blood pressure, while the renin-angiotensin system plays a minor or no role.

Vasopressin-mediated blood pressure response to intraventricular injection of angiotensin II in the rat.

1. The role of stimulation of argininevasopressin (AVP) release in the blood pressure (BP) response to intracerebroventricular (ivt) injection of angiotensin II (AII) was investigated. 2. Ivt injection of AII to normal Long-Evans (LE) rats, which were conscious and unrestrained, induced a dose-related increase of BP in close correlation with the rise of plasma AVP concentrations (r=0.93;y=34.0 log X-14.4). This regression line crossed the X-axis at plasma AVP concentrations found under control conditions. 3. In comparison with the correlation obtained after intravenous injection of AVP (r=0.99;y=35.6 log X-46.9), the correlation between BP increase and plasma AVP after ivt AII exhibited a parallel shift to the left by a factor of 7.5. 4. When 0.5 ml of a specific AVP antiserum was injected intravenously, the BP response to subsequent ivt injection of AII was completely blocked in 2 of 7 rats tested and reduced by 50% or more in the other 5 rats. 5. In Brattleboro rats homozygous for hereditary hypothalamic diabetes insipidus (DI), in which plasma AVP remained undetectable after ivt AII, BP response was reduced by 50–80% in comparison with the response in LE rats. Drinking response, however, was not altered. During spontaneous drinking, DI rats showed a BP increase of similar magnitude as that after the highest dose of ivt AII. 6. We conclude that a close relationship exists in normal LE rats between the rise of BP and of plasma AVP after ivt AII; this correlation represents a cause-effect relationship, since after the intravenous injection of AVP antiserum the BP response to ivt AII is markedly or completely blocked; and sensitization to the vasopressor effect of AVP occurs after ivt AII. The BP increase observed in unrestrained DI rats after ivt AII as well as during spontaneous drinking might be related to a general arousal reaction which would be insignificant in normal LE rats.

Plasma vasopressin concentrations and effects of vasopressin antiserum on blood pressure in rats with malignant two-kidney Goldblatt hypertension.

Male Sprague-Dawley rats with unilateral renal artery stenosis and a contralateral untouched kidney develop a malignant hypertension (MH) which is characterized by high blood pressures, sodium and water depletion, and subsequent activation of the renin-angiotensin system. In the present studies we found plasma arginine vasopressin (AVP) concentrations-3-fold higher than those in rats with benign renal hypertension, and 4- to 5-fold higher than those in normotensive control rats. Analysis of individual values showed considerable scatter; about 50% of the values fell in the range of benign hypertensive or control rats. When a specific AVP antiserum was injected, iv, into eight conscious unrestrained MH rats, BP transiently fell toward control values in four; in one, BP fell by only 10 mm Hg, and three other MH rats showed no response. In the same rats, injection of a specific angiotensin II antiserum always induced a transient fall in BP. On the basis of these and previously reported observations, we conclude that, subsequent to sodium and water loss and activation of the renin-angiotensin system, vasopressin release is stimulated in a significant number of MH rats and that, in these rats, vasopressin may cause significant systemic vasoconstriction. Thereby vasopressin may contribute to the development of malignant renal hypertension in rats.