Central Vasopressin Research Articles

901-111 ACE Inhibition (Quinapril) Modulates Central Vasopressin in the Rat

The beneficial effects of ACE inhibitors (ACEI) in heart failure and hypertension appear to be mediated not only by their influence on circulating ACE or tissue ACE in the heart. Previous studies have also implicated the brain as a possible site of actions for ACEI, e.g. by modifying central cardiovascular mechanisms. Their effects on central vasopressin (AVP), which is an important neurotransmitter in central cardiovascular regulation, are not known. Following chronic administration of Quinapril (6 mg/kgBW; 6 weeks, p.o.) ACE activity (in vitro autoradiography using a specific ACE inhibitor [ 125 I]351A) was markedly inhibited in the thalamus (38%), hypothalamus (37%), hypophysis (35%), cerebellum (36%) and plexus choroideus (20%) suggesting Quinapril may cross the blood brain barrier after chronic treatment. To study the influence of ACEI on central vasopressin, we determined the AVP content of 19 microdissected brain areas in rats treated with Quinapril. Regarding the hypothalamic AVP-producing nuclei, increased AVP levels could only been demonstrated in the paraventricular (PVN; Quinapril: 292 ± 197 vs. 2209 ± 568 pg/mg protein of controls; p < 0.001), but not in the supraoptic (SON) and the suprachiasmatic nucleus (SCN). Interestingly, vasopressin synthesizing cells in the PVN project not only to the posterior pituitary (like SON), but also to the lower brain stem and the spinal cord suggesting an important role of the PVN in the regulation of the cardiovascular system. Also, AVP content was sign, reduced in the median eminence (15643 ± 9240 vs. 28321 ± 4969, p < 0.001), where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Furthermore, sign, changes were registered in the central amygdala, inthesubcommissural organ and dorsal raphe nucleus. Autoradiographic study in vitro indicates that after chronic treatment Quinapril is able to cross the blood brain barrier and suppress central ACE activity. ACE inhibition with Quinapril markedly influences vasopressin in important brain areas which are involved in central cardiovascular regulation. Therefore, central modulatory effects of ACE inhibitor may contribute to their overall therapeutic efficacy.

Effect of chronic hyponatremia on central and peripheral oxytocin and vasopressin secretion in rats.

Previous studies have shown that many treatments that stimulate the peripheral secretion of oxytocin (OT) and vasopressin (AVP) from the pituitary simultaneously increase the levels of these peptides in the cerebrospinal fluid (CSF). Since osmotically and nonosmotically stimulated pituitary secretion of OT and AVP is markedly blunted in hyponatremic rats, the present studies evaluated whether central OT and AVP secretion into the CSF is similarly inhibited during sustained hyponatremia. Adult male rats with indwelling cisterna magna cannulae were rendered hyponatremic (plasma [Na+] < 110 mmol/l) by s.c. infusion of desmopressin (dDAVP; 10 ng/h) in combination with ingestion of a liquid diet for 3 days, then subjected to osmotic (i.v. or i.p. injection of 2 M NaCl; HS) or nonosmotic (6 mmol/kg of 0.15 M LiCl i.p.) stimulation. In normonatremic rats both i.v. and i.p. HS caused marked increases in plasma OT and AVP levels 30 min after treatment. Significant elevations of OT, but not AVP, were also present in CSF. Despite similar increases in plasma Na+ concentrations, plasma OT responses in the hyponatremic rats were absent after HS i.v. and were significantly blunted after HS i.p., but neither group had increased plasma AVP. In parallel with the plasma results, CSF OT responses were absent in hyponatremic rats given HS i.v. and significantly blunted in hyponatremic rats given HS i.p., but neither group had increased CSF AVP. Nonosmotic stimulation with isotonic LiCl increased OT levels both in plasma and CSF in normonatremic rats 20 min after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of an intracerebroventricularly administered vasopressin V1 antagonist on blood pressure and heart rate in deoxycorticosterone-salt hypertensive rats

It is well known that peripheral vasopressin (VP) is essential for the development and maintenance of DOC-salt hypertension. It is, however, still unclear whether central VP is involved in this type of hypertension. Therefore, the aim of this study was to clarify the role of central VP in the regulation of blood pressure in DOC-salt hypertension. In order to examine this issue, three series of investigations were performed. First, a novel vasopressin V1 antagonist (OPC21268) was administered intravenously to DOC-salt hypertensive rats, and mean arterial blood pressure (MABP) and heart rate (HR) were recorded. Second, the concentration of VP in the perfusate of microdialysis of cerebrospinal fluid (CSF) was determined in DOC-salt hypertensive and control rats. Finally, intracerebroventricular (i.c.v.) administration of a V1 antagonist was performed in DOC-salt hypertensive rats to determine the central mechanism of hypertension. Intravenous administration of a V1 antagonist had no effect on MABP and HR. There was no difference in VP in the perfusate of CSF between DOC-salt hypertensive and control rats. I.c.v. administration of a V1 antagonist significantly decreased MABP and HR in a dose-dependent manner in DOC-salt hypertensive rats ( P < 0.05-0.01). These results suggest that central VP is involved in the maintenance of DOC-salt hypertension, and the mechanism is, in part, mediated by upregulation of the V1 receptor.

Alteration of the physiological responses to indomethacin by endotoxin tolerance in the rat: a possible role for central vasopressin.

1. Previous studies suggest that arginine vasopressin (AVP) is released into the ventral septal area (VSA) of the rat brain during the antipyresis induced by the cyclo-oxygenase inhibitor indomethacin. In addition, there is evidence for increased AVP transmission in the VSA of animals having a reduced pyretic response following three intravenous injections of bacterial endotoxin (LPS) (endotoxin tolerant). Since ventral septal AVP receptors can also become 'sensitized' following exposure to AVP, we questioned whether the antipyretic action of indomethacin would increase, via an action involving central AVP, if this drug were administered into LPS-tolerant rats. 2. Intraperitoneal indomethacin (7.5 mg kg-1) was effectively antipyretic when administered 2 h after an intravenous challenge with LPS (50 micrograms kg-1) into conscious unrestrained rats. This dose of indomethacin had no effect on the core temperature of non-febrile rats given intravenous 0.9% pyrogen-free saline. 3. Three intravenous injections of LPS over a period of 3 days resulted in rats that were tolerant to the pyrogenic effects of LPS. When indomethacin was administered 2 h following the third LPS injection, a dose-dependent hypothermia was observed. This effect was age dependent, as profound hypothermia was seen in 8 week but not 20 week old rats. 4. A mortality rate of 41% (P = 0.02) was observed within 24 h of indomethacin treatment in 8 week old tolerant rats compared with 0% in 8 week old non-tolerant and 20 week old tolerant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential regulation of central vasopressin in transgenic rats harboring the mouse Ren-2 gene.

The transgenic (TG) rat carrying the mouse renin gene (mRen-2d) has provided a unique opportunity to explore central interactions between the brain renin-angiotensin (RAS) and vasopressin (AVP) systems. To evaluate the hypothalamic vasopressin axis in the TG rat, we measured the central nervous system concentrations of AVP and determined the effect of angiotensin II (ANG II) and its NH2-terminal heptapeptide [angiotensin-(1-7)] on blood pressure, heart rate, and AVP release using brain microdialysis. Intracerebroventricular infusion of ANG II or ANG-(1-7) in control rats increased local AVP release from the paraventricular and supraoptic nuclei. The ANG II infusion was associated with a significant increase in blood pressure not observed with ANG-(1-7). In contrast, the angiotensin peptide-induced central AVP responses and the ANG II-induced blood pressure increase were absent in the TG animal. The plasma AVP responses to ANG II and ANG-(1-7) were comparable in the control and TG rats. The TG rats exhibited a 22-fold higher level of AVP in the dorsal lower brain stem but had lower AVP levels in the posterior pituitary and the median eminence compared with control rats. These results suggest that insertion of the mouse renin gene into the rat genome leads to alterations in the AVP axis in terms of AVP peptide content and angiotensin-induced cardiovascular and AVP responses.

Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents

Central vasopressin pathways have been implicated in the mediation of paternal behavior, selective aggression, and affiliation in monogamous prairie voles. Here we demonstrate markedly different patterns of brain vasopressin receptor binding in the monogamous prairie vole and the congeneric nonmonogamous (promiscuous) montane vole. Vasopressin binding was assessed with both 3H-vasopressin and 125I-sarc-AVP using receptor autoradiography. The specificity of binding was consistent with a V1a receptor, the saturation kinetics were similar in the two species, and neither species showed evidence of sexual dimorphisms. In the prairie vole, highest specific binding was observed in the accessory olfactory bulb, diagonal band, laterodorsal thalamus, and superior colliculus. In the montane vole, specific binding was observed in the accessory olfactory bulb and superior colliculus as well, but in several other regions with high levels of binding in the prairie vole, binding was low or undetectable in the montane vole. In this nonmonogamous species, specific binding was high in lateral septum. Functional studies demonstrated the induction of phosphoinositol by AVP in the septum of the montane vole but not in the prairie vole. The pattern of 125I-sarc-AVP binding to lateral septum may reflect the social organization of these two species, as similar differences in AVP receptor distribution in the lateral septum were also observed in two related species, pine voles and meadow voles, which are monogamous and nonmonogamous, respectively. These results, along with earlier studies of AVP's effects on pair bonding, suggest the importance of this neuropeptide for the mediation of behaviors related to social organization.

Central cardiovascular effects of AVP and ANP in normotensive and spontaneously hypertensive rats

The purpose of the present study was to compare influence of central arginine vasopressin (AVP) and of atrial natriuretic peptide (ANP) on control of arterial blood pressure (MAP) and heart rate (HR) in normotensive (WKY) and spontaneously hypertensive (SHR) rats. Three series of experiments were performed on 30 WKY and 30 SHR, chronically instrumented with guide tubes in the lateral ventricle (LV) and arterial and venous catheters. MAP and HR were monitored before and after i.v. injections of either vehicle or 1, 10 and 50 ng of AVP and 25, 125 and 500 ng of ANP. Sensitivity of cardiac component of baroreflex (CCB), expressed as a slope of the regression line was determined from relationships between systolic arterial pressure (SAP) and HR period (HRp) during phenylephrine (Phe)-induced hypertension and sodium nitroprusside (SN)-induced hypotension. CCB was measured before and after administration of either vehicle, AVP, ANP, or both peptides together. Increases of MAP occurred after LV administration of 1, 10 and 50 ng of AVP in WKY and of 10 and 50 ng in SHR. ANP did not cause significant changes in MAP in both strains as compared to vehicle, but it abolished AVP-induced MAP increase in WKY and SHR. CCB was reduced in WKY and SHR after LV administration of AVP during SN-induced hypotension. In SHR but not in WKY administration of ANP, AVP and ANP + AVP decreased CCB during Phe-induced MAP elevation. The results indicate that centrally applied AVP and ANP exert differential effects on blood pressure and baroreflex control of heart rate in WKY and SHR and suggest interaction of these two peptides in blood pressure regulation at the level of central nervous system.

Role of central vasopressin in cardiovascular regulation: effect of dehydration and sex.

The present study was performed to evaluate the role of central vasopressin in cardiovascular regulation. First, a novel vasopressin V1 antagonist (OPC21268) was injected intracerebroventricularly in conscious rats. In water-deprived animals, the mean arterial blood pressure (MABP) and heart rate were significantly decreased compared with euhydrated control rats. There was, however, no significant difference in the concentration of vasopressin in the perfusate of cerebrospinal fluid between groups. Second, vasopressin was intracerebroventricularly injected in male and female homozygous Brattleboro rats. The increase in MABP was greater in males than in females. These results suggest that central vasopressin is involved in blood pressure regulation in pathophysiological states.

Suppressive effect of central vasopressin on hyperglycemic response

Suppressive effect of central vasopressin on hyperglycemic response

Mild sustained effects of neonatal vasopressin and oxytocin treatment on brain growth and behavior of the rat

The lasting effects of a 9-day neonatal exposure to vasopressin and oxytocin were examined in the rat to discover if peptide administration results in organizational effects. When tested in young adulthood, brain growth, not body growth, appeared to be impaired. Basal and challenge tests of urine production, carried out to see the development of the hormonal antidiuretic function of vasopressin, revealed no lasting changes, and therefore did not confirm earlier findings of an induced mild polyurea. Behavioral testing of learning by making use of a one-trial step-through paradigm with a 24-h retention trial—a test that is sensitive to vasopressin—did not show impairments. Open field tests, however, showed enhanced emotionality in the vasopressin-treated females, as well as an initially increased ambulation in the males, and increased grooming in both sexes, the latter also having been reported to be induced by vasopressin administration in the septal areas. Oxytocin treatment did not produce lasting changes. Our conclusion, therefore, is that peripherally circulating vasopressin can affect the organizational development of the rat brain. It remains to be established whether this is an effect obtained through changes in the general peripheral physiology or a reflection of plasticity phenomena at the level of central vasopressin neurotransmission.

Induction of arousal in hibernating European hamsters ( Cricetus cricetus L.) by vasopressin infusion in the lateral septum

Vasopressin immunostaining in the lateral septum of the European hamster ( Cricetus cricetus L.) disappears in autumn, at the time of the first appearance of hypothermic periods characteristic to hibernation. Previous results have shown that chronic administration of vasopressin in the lateral septum during winter prevents the expression of hypothermic periods, suggesting a role for this peptide in hibernation. It is now observed that acute infusion of vasopressin, and in 50% of the cases, of a specific vasopressin V 1 receptor agonist, during a hypothermic period results in an immediate termination of hypothermia. Infusion of oxytocin or a vasopressin V 2 receptor agonist were without effect. The results indicate that the seasonal variation in central vasopressin activity, possibly through an interaction with V 1 receptors, may play an important role in the expression of hibernation in the European hamster.

A role for central vasopressin in pair bonding in monogamous prairie voles.

Monogamous social organization is characterized by selective affiliation with a partner, high levels of paternal behaviour and, in many species, intense aggression towards strangers for defence of territory, nest and mate. Although much has been written about the evolutionary causes of monogamy, little is known about the proximate mechanisms for pair bonding in monogamous mammals. The prairie vole, Microtus ochrogaster, is a monogamous, biparental rodent which exhibits long-term pair bonds characterized by selective affiliation (partner preference) and aggression. Here we describe the rapid development of both selective aggression and partner preferences following mating in the male of this species. We hypothesized that either arginine-vasopressin (AVP) or oxytocin (OT), two nine-amino-acid neuropeptides with diverse forebrain projections, could mediate the development of selective aggression and affiliation. This hypothesis was based on the following observations: (1) monogamous and polygamous voles differ specifically in the distribution of forebrain AVP and OT receptors; (2) AVP innervation in the prairie vole brain is sexually dimorphic and important for paternal behaviour; (3) central AVP pathways have been previously implicated in territorial displays and social memory; and (4) central OT pathways have been previously implicated in affiliative behaviours. We now demonstrate that central AVP is both necessary and sufficient for selective aggression and partner preference formation, two critical features of pair bonding in the monogamous prairie vole.

The role of central vasopressin in the development of stress-induced gastric ulcer.

Annals of the New York Academy of SciencesVolume 689, Issue 1 p. 597-599 The Role of Central Vasopressin in the Development of Stress-Induced Gastric Ulcer KAZUFUMI HONDA, Corresponding Author KAZUFUMI HONDA Department of Medicine Jichi Medical School 3311-1, Kawachi-gun Tochigi 329-04, JapanAddress correspondence to: Kazufumi Honda, Department of Medicine, Division of Endocrinology and Metabolism, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi-ken 329-04, Japan.Search for more papers by this authorSAN-E ISHIKAWA, SAN-E ISHIKAWA Department of Medicine Jichi Medical School 3311-1, Kawachi-gun Tochigi 329-04, JapanSearch for more papers by this authorTOSHIKAZU SAITO, TOSHIKAZU SAITO Department of Medicine Jichi Medical School 3311-1, Kawachi-gun Tochigi 329-04, JapanSearch for more papers by this author KAZUFUMI HONDA, Corresponding Author KAZUFUMI HONDA Department of Medicine Jichi Medical School 3311-1, Kawachi-gun Tochigi 329-04, JapanAddress correspondence to: Kazufumi Honda, Department of Medicine, Division of Endocrinology and Metabolism, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi-ken 329-04, Japan.Search for more papers by this authorSAN-E ISHIKAWA, SAN-E ISHIKAWA Department of Medicine Jichi Medical School 3311-1, Kawachi-gun Tochigi 329-04, JapanSearch for more papers by this authorTOSHIKAZU SAITO, TOSHIKAZU SAITO Department of Medicine Jichi Medical School 3311-1, Kawachi-gun Tochigi 329-04, JapanSearch for more papers by this author First published: July 1993 https://doi.org/10.1111/j.1749-6632.1993.tb55602.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume689, Issue1The Neurohypophysis: A Window on Brain FunctionJuly 1993Pages 597-599 RelatedInformation

Renal and central vasopressin receptors: immunocytochemical localization.

Employing an anti-vasopressin monoclonal antibody for immunization, anti-idiotypic monoclonal antibodies were obtained which induced plasminogen activator production in the renal epithelial cell line LLC-PK1. The anti-idiotypic antibodies were employed to visualize vasopressin receptors on LLC-PK1 and A7r5 smooth muscle cells by immunofluorescence. All results indicated specificity of the anti-idiotypes for both V1 and V2 vasopressin receptor subtypes. These antibodies were used for immunohistochemical localization of vasopressin receptors in rat and bovine kidney preparations. In accordance with earlier physiological and biochemical observations, vasopressin receptors were detected predominantly in collecting ducts in cortex and medulla. On the cellular level, a differential staining pattern was observed. On rat brain tissue sections, dense staining was observed within various circumventricular organs. The staining pattern corresponded to that obtained in autoradiographic studies with labeled AVP(4-9) fragment peptide and differed from the distribution of binding sites for labeled vasopressin or V1 antagonists.

Atrial natriuretic peptide-induced effects are not dependent on intact central vasopressin secretion in conscious, fluid-balanced rats.

Atrial natriuretic peptide-induced effects are not dependent on intact central vasopressin secretion in conscious, fluid-balanced rats.

Effects of central vasopressin administration to infant rats

The neurohypophyseal peptide hormone arginine-vasopressin functions as a neuropeptide in several brain areas in addition to its role as a posterior pituitary hormone. Several studies indicate that arginine-vasopressin and arginine-vasopressin receptors appear early in the infant rat brain. To determine if arginine-vasopressin receptors in the infant were responsive to exogenous peptides, we compared the behavioral effects of central or peripheral administration of arginine-vasopressin, arginine vasotocin, the oxytocin precursor oxytocin-Gly-Lys-Arg, and arginine-vasopressin receptor antagonists in socially isolated rat pups. Central administration of arginine-vasopressin decreased the number of rat pup ultrasonic vocalization, reduced locomotor activity and decreased the latency to express a response to negative geotaxis. Temperature was also reduced at all doses tested. Co-administration of arginine-vasopressin and receptor antagonists suggested that changes in vocal behavior were mediated by the V 1 receptor subtype. Changes in core temperature appeared to be mediated by a V 2 receptor subtype. Peripheral arginine-vasopressin administration increased calling and decreased core body temperature. Neither effect was blocked by central receptor antagonist administration. The results are consistent with the hypothesis that arginine-vasopressin receptors in the infant rat brain are functional.

Suppression by central AVP of prostaglandin E1 hyperthermia in one-kidney, one-clip Goldblatt hypertensive rats

We have investigated the ability of the one-kidney, one-clip (1K,1C) hypertensive rat to develop a hyperthermic response to intracerebroventricular injection of prostaglandin (PG) E1. Accordingly, core temperature was monitored in response to PGE1 injections both preoperatively and on days 4, 8, 12, and 18 after either unilateral nephrectomy or the induction of hypertension due to nephrectomy plus renal artery clipping. Temperature responses to PGE1 were similar throughout each test day in normotensive, unilaterally nephrectomized control rats. In contrast, 1K,1C rats became hypertensive within 4 days of renal artery clipping, and at this time the hyperthermic response to PGE1 was virtually abolished. A reduced hyperthermic response was also seen at 8 and 12 days after clipping; by 18 days responses were again similar to controls. To determine whether central arginine vasopressin (AVP) was involved in the suppression of the hyperthermic response, we pretreated other hypertensive rats centrally with the V1-AVP antagonist [d(CH2)5Tyr(Me)]AVP before PGE1 injection. In 1K,1C animals thus treated, temperature responses 4-12 days after clipping were indistinguishable from those of similarly treated normotensive control rats. We suggest that the reduced hyperthermic responses to PGE1 seen in the 1K,1C rats during the initial development of hypertension may be due to activation of brain AVP pathways.

A critical role for central vasopressin in regulation of fever during bacterial infection.

Previous investigations on the antipyretic properties of arginine vasopressin have used bacterial endotoxins or pyrogens to induce fever. Because these experimental models of fever fail to mimic all aspects of the responses to infection, we felt it was important to examine the role of endogenously released vasopressin as a neuromodulator in febrile thermoregulation during infection. Therefore the present study examines the effects of chronic infusion of a V1-receptor antagonist or saline (via osmotic minipumps into the ventral septal area of the brain) on a fever induced by injection of live bacteria. Telemetry was used for continuous measurement of body temperature in the awake unhandled rat. Animals infused with the V1-antagonist exhibited fevers that were greater in duration compared with those of saline-infused animals. These results support the hypothesis that vasopressin functions as an antipyretic agent or fever-reducing agent in brain. Importantly, they suggest that endogenously released vasopressin may play a role as a neuromodulator in natural fever.

Attenuated development of ischemic brain edema in vasopressin-deficient rats.

Brain edema formation was investigated in the vasopressin-deficient Brattleboro rat using a middle cerebral artery occlusion model of early ischemic injury. Water and sodium accumulation after 4 h of ischemia were attenuated 36 and 20%, respectively, in the Brattleboro strain as compared to the control Long-Evans strain. This effect was independent of differences in animal size and state of hydration. In addition, measurements of cerebral blood flow indicated that Brattleboro and Long-Evans rats had equal levels of ischemia following middle cerebral artery occlusion. Systemic treatment of Brattleboro rats with vasopressin normalized their serum electrolyte concentrations and osmolarity but did not alter sodium or water accumulation in the ischemic brain. In contrast, intraventricular administration of vasopressin in Brattleboro rats increased edema formation to that seen in control rats. The reduced water and sodium accumulation in Brattleboro rats subjected to middle cerebral artery occlusion may be related to alterations in blood-brain barrier permeability since the blood-to-brain sodium flux was 36% less in the ischemic tissue of the Brattleboro as compared to the Long-Evans strain. These results support the hypothesis that central vasopressin is a regulator of brain volume and electrolyte homeostasis. Furthermore, our findings suggest a role for central vasopressin in the development of ischemic brain edema.

Chronic cardiovascular effects of central vasopressin in conscious rats.

To clarify the cardiovascular effects of central vasopressin (AVP), a chronic intracerebroventricular (ICV) infusion of AVP was performed in conscious Wistar normotensive rats. Animals were divided into 3 groups: 1) AVP 1 ng/hr (Low), 2) AVP 100 ng/hr (High), and 3) saline (control) ICV infusion. After a 6 day control period, AVP or saline was continuously infused into the lateral cerebroventricle at a rate of 1 microliter/hr using osmotic minipump for 7 days. As a result, a dose-related elevation of AVP concentration in CSF was achieved. Systolic blood pressure in both Low and High AVP infusion was slightly (7-12 mmHg) but significantly higher than that in control. ICV infusion of AVP did not alter urine volume, electrolytes excretion or osmolality, and AVP vascular antagonist injected intravenously failed to affect mean arterial pressure. Furthermore, plasma catecholamines and renin activity did not differ significantly among the groups. Thus, chronic ICV infusion of AVP induced the elevation of blood pressure, which is due to centrally mediated effect of AVP.