Arginine Vasopressin In Rats Research Articles

Centrally Administered Murine-Leptin Stimulates the Hypothalamus-Pituitary- Adrenal Axis through Arginine-Vasopressin

Starvation induces a decrease in circulating leptin levels and activation of the hypothalamus-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis in unfed rodents or genetically leptin-deficient ob/ob mice, whereas it stimulates corticotropin-releasing hormone (CRH) gene expression in the paraventricular nucleus (PVN). However, the interactions between leptin, CRH and the HPA axis are poorly understood and are likely to be complex. We recently demonstrated that central leptin administration caused increases in plasma arginine-vasopressin (AVP) and AVP gene expression of the PVN in nonstressful rats. AVP stimulates the release of adrenocorticotropic hormone (ACTH), but it also potentiates the action of CRH on ACTH release. In this study, we investigated the effects of leptin on plasma ACTH and corticosterone levels, CRH mRNA of the PVN and proopiomelanocortin (POMC) mRNA of the pituitary in nonstrained rats. Intracerebroventricularly administered leptin caused increases in plasma ACTH and corticosterone levels in dose-dependent manners. In Northern blot analyses, the leptin injection induced significant increases in the expression of CRH mRNA in the PVN and POMC mRNA in the pituitary. The increased plasma ACTH and corticosterone levels by leptin were attenuated with intracerebroventricular pretreatment of a V_1a receptor antagonist (OPC-21268) or a V_1a/V_1b receptor antagonist (dP[Tyr(Me)²]AVP), but not with that of a V₂ receptor antagonist (OPC-31260). The leptin-induced CRH mRNA expression in the PVN and POMC mRNA expression in the pituitary were also reduced by the pretreatment with OPC-21268 and dP[Tyr(Me)²]AVP. These results suggest that intracerebroventricular leptin administration activates the HPA axis by AVP receptor activation through V_1a receptors in the PVN which in turn activates CRH neurons to drive ACTH and corticosterone secretion in concert with AVP in nonstrained rats.

CHLOROQUINE INHIBITS ARGININE VASOPRESSIN PRODUCTION IN ISOLATED RAT INNER MEDULLARY SEGMENTS INDUCED cAMP COLLECTING DUCT

Previous studies showed that acute chloroquine administration increases plasma arginine vasopressin (AVP) concentration in the rat without influencing urine flow rate. The present study was designed to investigate whether chloroquine inhibits the AVP-induced cAMP production that mediates the antidiuretic effects of vasopressin. Single inner medullary collecting duct (IMCD) segments were pre-incubated at 35°C for 10 min followed by 4 min at 37° C with combinations of AVP and/or chloroquine with 1 mM 3-isobutyl-I-methylxanthine (IBMX) and cAMP concentrations were measured by radioimmunoassay. To establish the possible site of interference in cAMP production IMCD segments were incubated in the presence of chloroquine and forskolin. Chloroquine at concentrations ranging from 10−9 M to 10−6 M did not affect cAMP production by comparison with control. However, AVP (10−8 M) and forskolin (10−6 M) significantly (p < 0.01) increased cAMP accumulation. Chloroquine at all concentrations significantly suppressed the AVP stimulated cAMP production (e.g., chloroquine (10−8 M) + AVP (10−8 M) 41±12 fmol/4 mm (n = 9 tubules vs. AVP (10−8 M) alone 82 ± 9 fmol/4 min/mm (n = 37 tubules. Chloroquine at all concentrations tested did not have any effect an forskolin-induced cAMP production. The data suggest that chloroquine inhibits the AVP induced cAMP production at the level of hormone/receptor complex. This possibly explains the previously reported lack of the normal antidiuretic responses of AVP in rats following chloroquine administration.

Changes of hypothalamic and plasma vasopressin in rats with deoxycorticosterone-acetate induced salt appetite

Mineralocorticoids play a predominant role in development of salt appetite and hypertension. Since vasoactive peptides could mediate the central effects of mineralocorticoids, we evaluated changes of immunoreactive (IR) arginine–vasopressin (AVP) in the paraventricular (PVN) and supraoptic (SON) hypothalamic nucleus during DOCA-induced salt appetite. In one model, rats having free access to water and 3% NaCl during 9 (prehypertensive stage) or 21 days (hypertensive stage) received DOCA (s.c., 10 mg/rat/in alternate days). A decrease in the IR cell area, number of IR cells and staining intensity was obtained in magnocellular PVN of rats treated during 9 days. After 21 days IR cell area and number of cells in the PVN also decreased, but staining intensity of remaining cells was normal. The same parameters were unchanged in the SON. In another model, animals treated with DOCA during 9 days had only access to 3% NaCl or water. The IR cell area in PVN and SON significantly increased in mineralocorticoid-treated and control animals, both drinking 3% NaCl. Staining intensity (PVN and SON) and number of IR cells (PVN) also augmented in DOCA-treated animals drinking salt respect of a group drinking water. Plasma AVP in rats treated with DOCA and offered salt and water, exhibited a 2–2.5 fold increase at the time of salt appetite induction. Plasma AVP was substantially higher in rats drinking salt only, while the highest levels were present in salt-drinking DOCA-treated rats. Thus, peptide depletion in the PVN may be due to increased release, because reduced levels of hypothalamic and posterior pituitary AVP were measured in this model. In rats drinking salt only the substantial increase of IR AVP in the PVN and SON, may be due to dehydration and hyperosmosis. Because DOCA-salt treated rats showed higher AVP levels in the PVN compared to untreated rats drinking salt only, it is possible that DOCA sensitized PVN cells to increase AVP production. The results suggest the vasopressinergic system could mediate some central functions of mineralocorticoids.

Enhanced renal vasoconstrictor responsiveness to vasopressin after renal denervation.

Previous studies from our laboratory and others demonstrated a relative insensitivity of the renal vasculature to the vasoconstrictor influences of arginine vasopressin (AVP). Experiments were therefore conducted to identify the possible roles of renal sympathetic withdrawal and V2-vasopressinergic receptor-mediated vasodilation in this response. Renal hemodynamic responses to AVP or saline vehicle were examined in the presence or absence of either selective V1-vasopressinergic-receptor blockade or nonselective vasopressinergic-receptor antagonism in conscious intact and renal-denervated rats. Our results indicate that renal denervation profoundly augmented AVP-induced renal vasoconstriction, whereas no differences were observed in the responses to V1-receptor blockade versus combined V1, V2-receptor antagonism. These findings are consistent with a role for renal sympathoinhibition in mediating the relative insensitivity of the renal bed to the vasoconstrictor effects of AVP in conscious rats but do not support a modulatory influence of V2-receptor activity in this response.

Swim stress triggers the release of vasopressin within the suprachiasmatic nucleus of male rats

The hypothalamic suprachiasmatic nucleus (SCN) is the predominant pacemaker of the mammalian brain that generates and controls circadian rhythms of various endocrine and behavioral processes. Different lines of evidence suggest that stress interferes with the maintenance of such rhythms. As a first approach to investigate whether the neuropeptide arginine vasopressin (AVP), which shows circadian rhythms of synthesis and release within the SCN, might contribute to this stress-induced alterations in circadian rhythms, we monitored acute effects of swim stress on the intra-SCN release of AVP in male rats by means of the microdialysis technique. A 10-min forced swimming session triggered a marked but relatively short-lasting increase in the intranuclear release of AVP (to approx. 440%). This effect was restricted to the area containing predominantly somata and dendrites of vasopressinergic neurons, since no changes in AVP release could be measured in one of their major projection areas, the nucleus of the dorsomedial hypothalamus. Our data provide evidence that the amount of AVP released within the SCN can vary widely not only in accordance with AVP's intrinsically regulated circadian rhythm but also in response to a physiologically relevant stressor. In this way, the neuropeptide may contribute to the regulation of endocrine and behavioral rhythms particularly in challenging situations associated with resettings of the endogenous clock.

Inhibition by (−)-Cicletanine of the Vascular Reactivity to Angiotensin II and Vasopressin in Isolated Rat Vessels

In pithed rats, the levorotatory (−)-enantiomer of cicletanine reduces the pressor responses to angiotensin II (AII) and also, to a lesser extent, those to arginine-vasopressin (AVP). Here we have attempted to characterize further these inhibitory effects by studies of isolated perfused rat kidney and mesenteric vascular beds. In the isolated rat kidney, (−)-cicletanine behaves as a noncompetitive antagonist of AII- and AVP-receptor stimulation, with K i values of 9.6 and 208 μmol/L respectively. In the isolated mesenteric vascular bed, (−)-cicletanine antagonized both AII dependent contractions with an inhibitory concentration (IC 50) of 54.0 ± 20.5 μmol/L (n = 6), and AVP dependent contractions with an IC 50 of 31.6 ± 5.0 μmol/L (n = 8). In conclusion, (−)-cicletanine antagonizes AII more effectively in rat kidney than in mesenteric vascular beds. Moreover, in rat kidney vascular beds (−)-cicletanine is more potent in blocking the pressor responses to AII than in blocking those to AVP. A selective blockade of AII induced contractions in kidney vascular beds can be one factor explaining both the greater antagonistic potency of (−)-cicletanine against AII compared with AVP in pithed rats, and the renal protective properties of cicletanine in both hypertensive and aged rats.

Enhancement of central pressor effect of AVP in SHR and WKY rats by intracranial NG-nitro- l-arginine

The aim of the present study was to find out whether brain nitroxidergic system may be involved in modulation of central cardiovascular effects of arginine vasopressin (AVP) in normotensive (WKY) rats and whether its regulatory effects are altered in spontaneously hypertensive (SHR) rats. Two series of experiments were performed on conscious WKY and SHR rats instrumented with the lateral cerebral ventricle (i.c.v.) cannula and with the femoral arterial catheters. In Series 1 (10 WKY, 7 SHR rats), i.c.v. application of 2.3 nmol (0.5 μg) of N G-nitro- l-arginine ( l-NNA), an inhibitor of NO synthesis, did not significantly affect baseline arterial blood pressure (MAP) and heart rate (HR). In WKY but not in SHR, i.c.v. administration of 5.8 nmol (1 μg) of l-arginine ( l-ARG) elicited a small, significant decrease of MAP ( P<0.05) which could be reversed by i.c.v. pretreatment with l-NNA. In Series 2 (7 WKY, 8 SHR), administration of 10 pmol of AVP (10 ng) resulted in significant pressor effect in both strains; MAP increase being significantly greater in SHR than in WKY rats ( P<0.05). I.c.v. pretreatment with l-NNA significantly intensified the pressor response to centrally applied AVP both in WKY ( P<0.01) and in SHR ( P<0.01) rats; the maximum increase of blood pressure to combined administration of l-NNA and AVP being significantly greater in SHR than in WKY rats. The results indicate existence of an interaction between the central vasopressinergic and nitroxidergic system in blood pressure regulation. It is suggested that centrally released AVP increases availability of nitric oxide in the brain cardiovascular regions, whereas NO plays a compensatory role by reducing central pressor effect of AVP. Effectiveness of this compensatory mechanism is enhanced in the SHR rats.

Ventilatory effects of angiotensin and vasopressin in conscious rats

Angiotensin II (ANG II) stimulates ventilation (V), when ventilatory baroreceptor reflexes are taken into account, and arginine vasopressin (AVP) causes baroreflex inhibition of V in conscious and anesthetized dogs. To study mechanisms of hormonal modulation of V, a conscious rat model was investigated. V and metabolism were measured during steady-state intravenous infusions of ANG II and AVP in Sprague-Dawley rats (mean arterial pressure (MAP) increased 20 mmHg (1 mmHg = 133.3 Pa)). These data were compared with observations during equal pressor infusions of phenylephrine (PE), an agent classically used to study baroreceptor reflexes. V, respiratory frequency (f), and tidal volume (Vt) were maintained during the increased MAP associated with ANG II infusions, a response identical with that reported in conscious dogs. However, unlike dogs, AVP infusion did not depress V and metabolism in rats. PE in conscious rats caused an unexpected increase in Vt and V in association with increased metabolism. None of the pressor agents affected breath timing when the latter was binned by breath f. Since there was no obvious baroreflex inhibition of V with AVP and PE, potential stimulatory effects of ANG II on respiration could not be discerned. As well, the ventilatory baroreceptor pressure threshold may be higher or adaptation of the reflex may be faster in conscious rats than in dogs.

Effect of vasopressin V1- and V2-receptor stimulation on blood pressure in DOCA-salt hypertensive rats.

We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR.

Control of renal medullary blood flow by vasopressin V1 and V2 receptors.

Experiments were performed in anesthetized renal-denervated rats to determine the contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the regulation of renal medullary blood flow. Renal medullary interstitial infusion of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1) significantly decreased outer medullary blood flow by 15% and inner medullary blood flow by 35%, as measured with implanted optical fibers for laser-Doppler flowmetry. Medullary interstitial infusion of equimolar doses of arginine vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased inner medullary blood flow by only 17%, a decrease significantly less than that during the infusion of the V1 agonist. These results were confirmed in videomicroscopy experiments on the exposed papilla, which demonstrated that the V1 agonist and AVP decreased descending and ascending vasa recta capillary red blood cell velocity and calculated blood flow, with greater decreases during infusion of the V1 agonist. In further laser-Doppler flowmetry studies, stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D-arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present experiments indicate that vasopressin V1 receptor stimulation serves to decrease renal medullary blood flow while V2 receptor stimulation appears to increase renal medullary blood flow; however, the net effect of AVP is to decrease renal medullary blood flow.

In vivo diuretic actions of renal vasopressin V1 receptor stimulation in rats

The specific vasopressin V1 receptor agonist (V1AG; [Phe2,Ile3,Orn8]vasopressin) was infused (2.0 ng.kg-1.min-1) into the renal medullary interstitial space to determine the effects of selective medullary V1 receptor stimulation on sodium and water excretion in normal rats. Responses were compared with those of arginine vasopressin (AVP) and vasopressin V2 receptor stimulation resulting from infusion of a V1 receptor antagonist with AVP. Medullary infusion of V1AG or AVP in euvolemic rats produced no changes in hemodynamics or glomerular filtration rate. V1AG increased urine flow > 60% in euvolemic rats, whereas no change was observed with AVP. This response could not be explained by a rise of arterial pressure or by volume retention. With V2 stimulation in euvolemic rats, urine flow was decreased. In water diuretic rats, V1AG produced no change, whereas AVP infusion decreased urine flow. The results provide in vivo evidence that tubular V1 vasopressin receptor activity results in increased urine flow and thereby modulates the antidiuretic actions of vasopressin in the euvolemic state.

In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC-31260, in conscious rats.

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist (5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine; OPC-31260) antagonizes the antidiuretic action of endogenous and exogenous AVP in conscious rats. OPC-31260, given orally at a dose of 5 mg/kg or higher, increased urinary volume (UV) and reduced urinary osmolality (Uosm) in a dose-dependent manner, in rats acutely denied access to water. Minimal Uosm was obtained 1-2 h after oral administration of OPC-31260. OPC-31260 caused sustained water diuresis for more than 12 h when water was available ad libitum since OPC-31260 (30 mg/kg) reduced Uosm to less than 230 mOsmol/kg H2O, significantly less than the control value of 600 mOsmol/kg H2O. Water deprivation for 24 h increased plasma AVP levels to 7.2 pmol/l and increased Uosm to 2160 mOsmol/kg H2O. In such water-deprived rats, oral administration of OPC-31260 at 100 mg/kg was diuretic; it markedly increased free water clearance and decreased Uosm to 202 mOsmol/kg H2O. In homozygous Brattleboro rats (with inherited AVP deficiency), given free access to water, subcutaneous infusion of the V2 agonist 1-deamino-8-D-AVP (dDAVP) at a rate of 1 ng/h markedly decreased UV to 12.6 from 148.7 ml/day and increased Uosm to 1762 from 231 mOsmol/kg H2O. OPC-31260 (30 mg/kg) promptly increased UV and reduced Uosm to levels similar to those before the administration of dDAVP; repeated OPC-31260 treatment had sustained effects. These results indicate that OPC-31260 is an orally effective non-peptide AVP antagonist to the antidiuretic action of AVP in the conscious rat.

Enhanced pressor responses to ICV vasopressin after pretreatment with oxytocin.

The role of oxytocin (OT) in the modulation of arginine vasopressin (AVP)-induced cardiovascular effects within the central nervous system was investigated in urethan-anesthetized rats. Intracerebroventricular injection of AVP (1-10 pmol) produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR). These responses were enhanced in rats pretreated 24 h earlier with OT (10 pmol icv). The enhanced cardiovascular effects of AVP in OT-pretreated animals were dose dependent, blocked by the V1 antagonist d(CH2)5Tyr(Me)AVP, not evoked by OT alone, and occurred in the absence of changes in basal (nonstimulated) MAP and HR. In addition, central administration of AVP in OT-pretreated rats, but not in saline-pretreated controls, caused dose-dependent oscillations of the MAP and HR responses and, at higher doses, death of the animals. The enhanced cardiovascular actions of centrally injected AVP in OT-pretreated rats do not appear to be secondary to skeletal muscle contractions or the result of cerebral ischemia. Our data point to an interaction between the central oxytocinergic and vasopressinergic systems in cardiovascular control.

Oxytocin Pretreatment Enhances Arginine Vasopressin‐lnduced Motor Disturbances and Arginine Vasopressin‐lnduced Phosphoinositol Hydrolysis in Rat Septum: A Cross‐Sensitization Phenomenon

The recent observation that the central oxytocin (OT) receptor has high affinity for both OT and arginine vasopressin (AVP) raises the possibility that it may be involved in some of the central actions of AVP. Repeated intracerebroventricular (icv) injections of AVP in rats evoke an unusual sensitization phenomenon in that a first exposure to the peptide enhances the sensitivity (sensitization) of the brain to a second exposure. This report investigates the possibility that the OT receptor may be involved in the mediation of the phenomenon of sensitization, using OT, a specific OT receptor agonist, [Thr4,Gly7]OT, and a specific OT receptor antagonist, d(CH2)5,[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (compound 6; cpd 6), as well as a V1 AVP receptor antagonist, d(CH2)5Tyr(Me)AVP. Peptides were injected icv in conscious, adult male Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist.

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.

Pressor actions of arginine vasopressin in pithed Sprague-Dawley, Wistar-Kyoto and spontaneously hypertensive rats before and after treatment with nifedipine or pertussis toxin.

The pressor actions of arginine vasopressin (AVP) were examined in pithed Sprague-Dawley and Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Prior to pithing, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded via an intra-arterial catheter from sodium pentobarbital anaesthetized rats. SBP and DBP recorded from SHR were significantly greater than those from Sprague-Dawley and WKY rats. However, after pithing, there were no significant differences between DBP among the various strains. Pertussis toxin pretreatment significantly reduced the prepithing SBP and DBP of the SHR but not Sprague-Dawley or WKY rats. Administration of nifedipine significantly reduced DBP of pithed rats. The dose-diastolic pressure response curves obtained from infusion of AVP in Sprague-Dawley and WKY rats were not significantly different from one another, but the maximal vasopressor responses to AVP in pithed SHR were enhanced. Administration of nifedipine to Sprague-Dawley and WKY rats did not affect the dose-response curve to AVP, but nifedipine administration in SHR led to a significant inhibition of the pressor responses to AVP. Furthermore, pertussis toxin pretreatment of rats significantly reduced a component of the AVP pressor effect in SHR but not Sprague-Dawley or WKY rats. We speculate that, in SHR, vasopressin receptors are coupled to a pertussis toxin-sensitive G protein that, in turn, may couple to a dihydropyridine-sensitive calcium channel and also to a pertussis-insensitive G protein that is probably coupled to the phospholipase C/intracellular calcium release process. A component of the elevated blood pressure in SHR is also regulated by a pertussis toxin-sensitive process.(ABSTRACT TRUNCATED AT 250 WORDS)

Septal and Hippocampal Release of Vasopressin and Oxytocin during Late Pregnancy and Parturition in the Rat

The push-pull perfusion technique, in conjunction with specific radioimmunoassays, was used to monitor the release of both arginine vasopressin (AVP) and oxytocin (OXT) within distinct limbic brain areas of conscious female rats. In pregnant rats near term, the release of AVP was greater than that of virgin rats in both the ventral (p less than 0.001) and mediolateral (p less than 0.001) septal areas; similarly, release of OXT increased in the ventral septal area (p less than 0.01) at this time. In contrast, no changes in the levels of either peptide occurred in the dorsal hippocampus. In parturient rats, AVP release tended to decrease in the septal areas but increased fivefold in the dorsal hippocampus (p less than 0.001) compared to pregnant animals. In contrast, OXT levels assayed in the same perfusates did not differ from those observed in pregnant animals. Plasma levels of AVP in pregnant rats (p less than 0.05) and of OXT in parturient animals (p less than 0.01) were found to be increased over levels in virgin rats. The regionally different and peptide-specific changes in release pattern of AVP and OXT in virgin, pregnant and parturient rats may be of physiological significance in antipyresis and behaviors accompanying parturition.

Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin in rats after several osmotic loads

Urinary digoxin-like immunoreactive factor (DLIF), arginine-vasopressin (AVP) and other urinary parameters were investigated under normal conditions and after the i.p. injection of the following solutions: distilled water, isotonic and hypertonic NaCl, NaHCO 3, KCl and urea, at a rate of 3 ml/100 g body weight. The measurement of digoxin-like immunoreactivity by two different radioimmunoassays showed that DLIF was stimulated by all volume loads regardless of the presence or absence of osmolar compounds. This dissociation between DLIF and urinary sodium excretion suggests that DLIF may not constitute the natriuretic hormone. Moreover, a dissociation between DLIF and AVP excretion also were found, which speaks against the hypothesis of a common mechanism of stimulation for both substances.

Area postrema and differential reflex effects of vasopressin and phenylephrine in rats

In normal rats, baroreflex inhibitions of heart rate (HR) and splanchnic but not lumbar sympathetic neural activity (SNA) are greater when mean arterial pressure (MAP) is increased by intravenous infusion of arginine vasopressin (AVP) compared with phenylephrine (PE) or methoxamine. In normal rabbits, baroreflex inhibitions of HR and lumbar and renal SNA are all greater when MAP is increased by AVP vs. PE. The differential reflex bradycardic and renal sympathoinhibitory effects of AVP vs. PE in rabbits require an intact area postrema. To determine whether differential reflex effects of AVP vs. PE in rats is selective for HR or inclusive of renal SNA and to examine the role of the rat area postrema in such action, we monitored HR and renal SNA in normal (sham operated, n = 8) and area postrema-lesioned (APX, n = 8) rats under chloralose anesthesia during slow increases in MAP (less than 0.3 mmHg/s; 3 min) induced intravenously by AVP (0-16 mU.kg-1.min-1) and by PE (0-8 micrograms.kg-1.min-1). Reflex inhibition of HR (-delta betas.min-1.delta mmHg-1) was greater when MAP was increased by AVP vs. PE in normal rats (-2.7 +/- 0.5 vs. -1.7 +/- 0.1, P less than 0.05), and this difference was absent in APX rats (-2.5 +/- 0.5 vs. +/- -2.2 +/- 0.4). Similarly, maximum bradycardia (-delta beats/min) by AVP vs. PE was greater in normal rats (-64 +/- 8 vs. -48 +/- 7, P less than 0.05) but not in APX rats (-53 +/- 5 vs. -52 +/- 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressinergic augmentation of cardiac baroreceptor reflex in conscious rats

Experiments were performed on conscious, chronically instrumented rats to determine the contribution of V2-receptor activation in augmentation of cardiac baroreceptor reflex (BRR) sensitivity by arginine vasopressin (AVP). At least 1 wk before experimentation, rats were implanted with arterial and venous catheters, as well as with pulsed Doppler flow probes for measurement of cardiac output (CO). An initial set of experiments was performed to determine whether cardiac BRR sensitivity is enhanced by AVP in conscious rats. A series of pressor doses of either AVP or phenylephrine (PE) were administered on separate days (n = 8). The slope of pulse interval (PI) vs. mean arterial blood pressure (MABP) was determined for each experiment by linear regression and used as an index of cardiac BRR sensitivity. The slope of PI vs. MABP was greater in response to AVP than in response to PE in all animals studied. A separate group of animals (n = 7) received either a 40-min infusion of AVP (5 ng/min iv) or a specific V2-antagonist, d(CH2)5[DIle2,Ile4]AVP (20 micrograms/kg iv), 10 min before infusion of AVP. The responses of MABP, CO, and total peripheral resistance to AVP infusion were similar with and without V2-antagonism; however, the bradycardic response to AVP was less with V2-antagonist pretreatment. Furthermore, administration of V2-antagonist reduced delta PI/delta MABP in response to AVP infusion. Additional experiments were performed to test the effect of infusion of a specific V2-agonist, dVDAVP (5 ng/kg iv), on BRR-induced bradycardia in response to a series of pressor PE bolus doses.(ABSTRACT TRUNCATED AT 250 WORDS)