Contribution of N-methyl-d-aspartate receptors in the anteroventral third ventricular region to vasopressin secretion,but not to cardiovascular responses provoked by hyperosmolality and prostaglandin E2 in conscious rats

The aim of this study is to pursue roles of N-methyl-d-aspartate (NMDA) receptors in the anteroventral third ventricular region (AV3V; a pivotal area for autonomic functions) in controlling vasopressin (AVP) release and cardiovascular system. In conscious rats, we examined effects of AV3V infusion of MK-801 (a selective antagonist for NMDA receptor) on plasma AVP, osmolality, electrolytes, arterial pressure and heart rate, in the absence or presence of NMDA, hyperosmotic or prostaglandin (PG) E2 stimulus. The AV3V infusion of NMDA caused significant increases in plasma AVP, osmolality and sodium, hematocrit, arterial pressure and heart rate after 5 or 15min. When NMDA was administered into the cerebral ventricle, relatively smaller elevations were observed only in plasma AVP and arterial pressure. The effects of AV3V infusion of NMDA were nearly completely prevented by MK-801 applied to the same region before 15min. The application of MK-801 was also potent to block rises of plasma AVP elicited by AV3V injection of PGE2 or i.v. infusion of hypertonic saline. However, it inhibited neither increases of arterial pressure and heart rate due to the PGE2 treatment nor those of arterial pressure, plasma osmolality and sodium in response to the osmotic load. Histological analysis on the AV3V infusion sites of NMDA, MK-801 and PGE2 indicated that they had been located in the structures such as the median and medial preoptic nuclei, periventricular nucleus and medial preoptic area. These results suggest that stimulation of AV3V NMDA receptors in the basal state may facilitate AVP secretion and cause pressor and tachycardiac actions, and that these receptors may be involved in both the hyperosmolality- and PGE2-induced hormone release, but not in the cardiovascular responses to these stimuli.     

Involvement of anteroventral third ventricular AMPA/kainate receptors in both hyperosmotic and hypovolemic AVP secretion in conscious rats

The area of the brain called the anteroventral third ventricular region (AV3V) includes three different subtypes of glutamate receptor, as well as neural circuits controlling fluid balance and cardiovascular and neuroendocrine functions. Although our previous data indicate the ability of AV3V N-methyl-d-aspartate (NMDA) and metabotropic receptors to provoke vasopressin (AVP)-releasing, pressor and hyperglycemic responses, the roles of non-NMDA receptors selective for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate have not been elucidated to date. To address this question, the effects of intracerebral infusion with FWD or NBQX (specific agonist and antagonist for non-NMDA receptors, respectively) on plasma AVP, glucose, osmolality, electrolytes and cardiovascular parameters were examined in conscious rats in the absence or presence of an osmotic or volemic stimulus. When applied topically to AV3V structures such as the median preoptic nucleus, FWD augmented plasma AVP, osmolality, glucose and arterial pressure in a dose-associated fashion. All responses of the variables were abolished by pre-administering NBQX, which exerted no conspicuous effect on any variable except arterial pressure. It was revealed that NBQX administration in AV3V structures such as the median preoptic nucleus and the periventricular nucleus inhibited the rise of plasma AVP in response to intravenous infusion with hypertonic saline or removal of systemic blood through the femoral artery. Elevation of plasma osmolality and sodium evoked by osmotic load, and elevation of plasma osmolality, glucose and angiotensin II and decrease of arterial pressure caused by bleeding, were not significantly affected by NBQX treatment. These results suggest that AV3V non-NMDA receptors, as well as NMDA receptors, may elicit AVP-releasing, pressor and hyperglycemic actions when stimulated in the basal state, and may facilitate AVP secretion under both hyperosmotic and hypovolemic conditions, without contributing to cardiovascular, blood glucose or other responses.     

Anteroventral third ventricular N-methyl-D-aspartate receptors, but not metabotropic glutamate receptors are involved in hemorrhagic AVP secretion

This study aimed to investigate the roles of glutamate (Glu) receptors in the anteroventral third ventricular region (AV3V), a pivotal area for water, cardiovascular and neuroendocrine regulations, in causing vasopressin (AVP) secretion and other phenomena in response to bleeding. The effects of intracerebral infusions of MK-801 [a N-methyl-D-aspartate (NMDA) receptor antagonist] or a metabotropic Glu receptor antagonist (MCPG) on plasma levels of AVP, electrolytes, osmolality and glucose, heart rate and arterial pressure following AV3V administration with NMDA or bleeding stimuli were analyzed in conscious rats. NMDA provoked prominent rises of plasma AVP, osmolality, glucose and arterial pressure, without changing plasma electrolytes or heart rate significantly. All the effects of NMDA were blocked by pre-administration of MK-801 into the same loci. Removal through a femoral arterial line of 10 ml blood per kg body weight did not affect arterial pressure or other variables significantly, although plasma AVP and angiotensin II (ANG II) tended to increase. When bleeding was repeated after 10 min (B2), arterial pressure dropped promptly, and plasma AVP, ANG II, osmolality and glucose augmented remarkably. MK-801 applied 35 min preceding B2, to loci such as the median preoptic nucleus, periventricular nucleus and medial preoptic area inhibited the response of plasma AVP significantly, without exerting any effects on other variables. When MK-801 was administered intracerebroventricularly, or when MCPG was infused into the AV3V, significant alterations did not occur in B2-evoked responses of plasma AVP nor in those of the other variables. In rats given sham bleeding after AV3V infusions of MK-801 or MCPG or intracerebroventricular applications of MK-801, all monitored variables roughly remained at stable levels throughout the experiments. We conclude that NMDA receptors in AV3V, but not metabotropic Glu receptors, may facilitate AVP secretion in hypotensive hypovolemia.     

Anteroventral third ventricular N-methyl-d-aspartate receptors, but not metabotropic glutamate receptors are involved in hemorrhagic AVP secretion

This study aimed to investigate the roles of glutamate (Glu) receptors in the anteroventral third ventricular region (AV3V), a pivotal area for water, cardiovascular and neuroendocrine regulations, in causing vasopressin (AVP) secretion and other phenomena in response to bleeding. The effects of intracerebral infusions of MK-801 [a N-methyl-D-aspartate (NMDA) receptor antagonist] or a metabotropic Glu receptor antagonist (MCPG) on plasma levels of AVP, electrolytes, osmolality and glucose, heart rate and arterial pressure following AV3V administration with NMDA or bleeding stimuli were analyzed in conscious rats. NMDA provoked prominent rises of plasma AVP, osmolality, glucose and arterial pressure, without changing plasma electrolytes or heart rate significantly. All the effects of NMDA were blocked by pre-administration of MK-801 into the same loci. Removal through a femoral arterial line of 10 ml blood per kg body weight did not affect arterial pressure or other variables significantly, although plasma AVP and angiotensin II (ANG II) tended to increase. When bleeding was repeated after 10 min (B2), arterial pressure dropped promptly, and plasma AVP, ANG II, osmolality and glucose augmented remarkably. MK-801 applied 35 min preceding B2, to loci such as the median preoptic nucleus, periventricular nucleus and medial preoptic area inhibited the response of plasma AVP significantly, without exerting any effects on other variables. When MK-801 was administered intracerebroventricularly, or when MCPG was infused into the AV3V, significant alterations did not occur in B2-evoked responses of plasma AVP nor in those of the other variables. In rats given sham bleeding after AV3V infusions of MK-801 or MCPG or intracerebroventricular applications of MK-801, all monitored variables roughly remained at stable levels throughout the experiments. We conclude that NMDA receptors in AV3V, but not metabotropic Glu receptors, may facilitate AVP secretion in hypotensive hypovolemia.     

Roles of forebrain GABA receptors in controlling vasopressin secretion and related phenomena under basal and hyperosmotic circumstances in conscious rats

Although the anteroventral third ventricular region (AV3V), a forebrain area essential for homeostatic responses, includes receptors for γ-aminobutyric acid (GABA), the roles of these receptors in controlling vasopressin (AVP) secretion and related phenomena have not been clarified as yet. This study aimed to pursue this problem in conscious rats implanted with indwelling catheters. Cerebral injection sites were determined histologically. Applications of bicuculline, a GABA_A receptor antagonist, to the AV3V induced prompt and marked augmentations in plasma AVP, osmolality, glucose, arterial pressure and heart rate, without affecting plasma electrolytes. Such phenomena did not occur when phaclofen, a GABA_B receptor antagonist, was applied to the AV3V. All of the effects of AV3V-administered bicuculline were abolished by preadministration of the GABA_A receptor agonist muscimol. Preadministration of either MK-801 or NBQX, ionotropic glutamatergic receptor antagonists, was also potent to abolish the AVP response to AV3V bicuculline. When hypertonic saline was infused intravenously, plasma AVP increased progressively, in parallel with rises in plasma osmolality, sodium and arterial pressure. AV3V application of muscimol or baclofen, a GABA_B receptor agonist, was found to abolish the response of plasma AVP, without inhibiting that of the osmolality or sodium. The response of arterial pressure was also blocked by muscimol treatment, but not by baclofen treatment. Based on these results, we concluded that, under basal conditions, GABA receptors in the AV3V or vicinity may tonically operate to attenuate AVP secretion and cardiovascular functions through mechanisms associated with glutamatergic activity, and that plasma hyperosmolality may cause facilitation of AVP release by decreasing forebrain GABAergic activity.     

A study on the mechanism by which sodium nitroprusside,a nitric oxide donor,applied to the anteroventral third ventricular region provokes facilitation of vasopressin secretion in conscious rats

We reported previously that sodium nitroprusside (SNP) applied to the anteroventral third ventricular region (AV3V), a pivotal area for autonomic functions, facilitates vasopressin (AVP) secretion in conscious rats. The aim of this study was to pursue the problems of whether nitric oxide (NO) generated from the agent may be responsible for the phenomenon, and whether it may be mediated by cyclic guanosine monophosphate (cGMP), the biosynthesis of which could reportedly be activated by NO. The infusion of SNP into the AV3V of conscious rats produced dose-related increases in plasma AVP, the maximal responses of which appeared at 5 min. Blood pressure and heart rate tended to rise at 15 min. The plasma osmolality, sodium, potassium or chloride did not show marked alteration following the SNP administration. Although the SNP solution was hypertonic and hypernatremic, AV3V application of hypertonic saline with a relatively higher osmolality and an equal sodium level was significantly less effective in augmenting plasma AVP. When injected into the lateral ventricle, SNP did not change plasma AVP and reduced arterial pressure, different from the results provoked by the AV3V application. The rise in plasma AVP in response to the AV3V application of SNP was diminished by preadministration of hemoglobin, a scavenger of NO, that did not affect the responses of the other variables. In contrast, pretreatment with methylene blue, an agent capable of antagonizing the potency of NO to activate guanylate cyclase, did not attenuate but potentiated the responses of both plasma AVP and arterial pressure to the AV3V infusion of SNP. Hemoglobin or methylene blue given alone into the AV3V did not affect any of the variables monitored. On the other hand, the AV3V injection of 8-bromo cGMP, a stable analogue of cGMP, was not potent for causing a significant rise in plasma AVP, in contrast to the notable AVP-enhancing effect of 8-bromo cAMP. Arterial pressure and heart rate were elevated by both of these agents, whereas the remaining variables were not altered. Histological inspection indicated that the infusion sites of the drugs in the AV3V had included areas such as the organum vasculosum of the lamina terminalis, median preoptic nucleus, medial preoptic nucleus and periventricular nucleus. On the basis of these results, we concluded that the AVP secretion prompted by the AV3V application of SNP may be attributable to NO, whereas its well-known ability to stimulate guanylate cyclase activity may hardly contribute to this phenomenon.     

Central neural pathway mediating splanchnic osmosensation

To determine the central neural pathway which carries splanchnic osmosensory information to vasopressin (AVP) neurons in the hypothalamus, bilateral electrolytic lesions were placed in the ascending catecholaminergic fiber bundle, the locus coeruleus (LC), the locus subcoeruleus (subLC), the lateral parabrachial nucleus (LPB), the caudal periaqueductal gray (PAG) and the median preoptic nucleus (MPO). Six and seven days later, plasma AVP levels, plasma osmolality, mean arterial pressure and heart rate were measured following gastric infusion of hypertonic (598 mosm/kg; 2ml/4min) or isotonic (290 mosm/kg) saline in conscious rats with indwelling tail artery catheters and nasogastric tubes. The most effective pontine lesions, which were located in the ventral locus subcoeruleus (vsubLC) approximately 1.0 mm below the LC, decreased the AVP response to hypertonic gastric infusion by 59.7% (P < 0.05) as compared to sham-lesioned controls. In addition, unilateral vsubLC lesions dramatically reduced the catecholamine innervation of the ipsilateral paraventricular nucleus (PVN), as qualitatively determined with dopamine β-hydroxylase immunocytochemistry, suggesting that a pathway ascending with catecholaminergic fibers was disrupted. Lesions of the MPO were also very effective, decreasing the AVP response to hypertonic saline infusion by 60.3% (P < 0.05), suggesting that the MPO is an integral relay center in this pathway. On the other hand, LC, LPB and PAG lesions were ineffective. Systemic plasma osmolality or cardiovascular factors did not mediate the AVP response. These results demonstrate, for the first time, that splachnic osmotic information is transmitted to the hypothalamus via pathways within the ascending catecholaminergic fiber bundles, the MPO is a relay center where peripheral and central osmotic information may be integrated, and the LC, LPB and PAG are not part of the splanchnic osmotic pathway.     

Anteroventral third ventricle (AV3V) lesion affects hypothalamic neuronal nitric oxide synthase (nNOS) expression following water deprivation

Neuronal nitric oxide synthase (nNOS) has been reported to be up-regulated in the hypothalamic supraoptic nucleus (SON) during dehydration which in turn could increase nitric oxide (NO) production and consequently affect arginine vasopressin (AVP) secretion. The anteroventral third ventricle (AV3V) region has strong afferent connections with the SON. Herein we describe our analysis of the effects of an AV3V lesion on AVP secretion, and c-fos and nNOS expression in the SON following dehydration. Male Wistar rats had their AV3V region electrolytically lesioned or were sham operated. After 21 days they were submitted to dehydration or left as controls (euhydrated). Two days later, one group was anaesthetized, perfused and the brains were processed for Fos protein and nNOS immunohistochemistry (IHC). Another group was decapitated, the blood collected for hematocrit, osmolality, serum sodium and AVP plasma level analysis. The brains were removed for measurement of neurohypophyseal AVP content, and the SON was punched out and processed for nNOS detection by western blotting. The AV3V lesion reduced AVP plasma levels and c-fos expression in the SON following dehydration (P<0.05). Western blotting revealed an up-regulation of nNOS in the SON of control animals following dehydration, whereas such up-regulation was not observed in AV3V-lesioned rats (P<0.05). We conclude that the AV3V region plays a role in regulating the expression of nNOS in the SON of rats submitted to dehydration, and thus may affect the local nitric oxide production and the secretion of vasopressin.     

Group I metabotropic glutamate receptor-mediated enhancement of dopamine cell burst firing in rat ventral tegmental area in vitro

Metabotropic glutamate receptor (mGluR) agonist t-ACPD produced concentration-dependent enhancement of NMDA/apamin-induced burst firing and membrane oscillations in dopamine cells, recorded intracellularly from ventral tegmental area in the rat midbrain slice. Such effects were blocked reversibly by mGluR antagonist MCPG, and mimicked by the selective agonist for group I (but not group II and III) mGluRs. Our results point out a selective involvement of group I mGluRs in facilitating burst firing of midbrain dopamine cells.     

Alterations in the central vasopressin and oxytocin axis after lesion of a brain osmotic sensory region

The anteroventral region of the third ventricle (AV3V) is critical in mediating osmotic sensitivity. AV3V lesions increase plasma osmolality and block osmotic-induced vasopressin (VP) and oxytocin (OT) secretion. The aim was to evaluate the effects of AV3V lesions on neurosecretion under control/water replete conditions and after 48 h dehydration. The focus was on central peptidergic changes with measurement of OT and VP content in the hypothalamic paraventricular (PVN) and supraoptic (OT) regions and the posterior pituitary. AV3V-lesioned rats exhibited an elevated plasma osmolality and higher OT content in SON and PVN. There was an increase in VP content in PVN, but no change in SON. As predicted, the plasma peptide response to dehydration was absent in lesioned animals. However, dehydration produced depletion in posterior pituitary VP in lesioned animals with no change in OT. No changes in nuclear VP and OT levels were seen after dehydration. These results demonstrate that AV3V lesions alter the VP and OT neurosecretory system, seen as a blockade of osmotic-induced release and an increase in basal nuclear peptide content. The data indicate that interruption of the osmotic sensory system affects the central neurosecretory axis, resulting in a backup in content and likely changes in synthesis and processing.     

Ventral pontine catecholaminergic pathway mediates the vasopressin response to splanchnic osmostimulation in conscious rats

This study examines the role of catecholamines, cell bodies and fibers of passage within the subcoeruleus area (subLC) in the arginine vasopressin (AVP) response to splanchnic osmotic stimulation and hemorrhage. Bilateral chemical lesions were induced into the subLC, approximately 1 mm ventral to the locus coeruleus (LC), using 6-hydroxydopamine (6-OHDA) and ibotenic acid to selectively destroy catecholaminergic components and cell bodies, respectively. Vehicle and 5,7-dihydroxytryptamine (5,7-DHT) injections into the subLC area, 6-OHDA injections into the LC, as well as systemic desipramine pretreatment, were performed as controls for the possible non-specific effects of the lesions. Seven and 8 days later, plasma AVP level, plasma osmolality, mean arterial pressure and heart rate were measured following either gastric infusion of hypertonic (598 mOsm/kg; 2 ml/4 min) or isotonic (290 mOsm/kg) saline or a mild hemorrhage (2.5 ml/300 g) in conscious rats with indwelling tail artery catheters and naso-gastric tubes. 6-OHDA injections into subLC reduced the AVP response to the osmotic stimulation by 62.3% ( P < 0.01), as compared to vehicle-injected controls. These same rats demonstrated a normal AVP response to hemorrhage implying a specificity of the disrupted pathway. All controls confirmed that the effects of the 6-OHDA were due to specific action on noradrenergic components within the subLC area. Ibotenic acid lesions in the subLC did not significantly decrease the AVP response, demonstrating that mainly fibers and not cell bodies in this region are part of the pathway. 6-OHDA injections just anterior to the LC, where the dorsal noradrenergic bundle (DNAB) forms, reduced the AVP secretion due to hemorrhage by 77.0%% (P < 0.05), but had minor effects on the response to osmotic stimulation. These results indicate that catecholaminergic fibers travelling primarily within the subLC, in the ventral noradrenergic bundle (VNAB), carry splanchnic osmotic input to the hypothalamus, whereas the DNAB may mediate the AVP response to hemorrhage.     

Vasopressin reduces release from vasopressin-neurons and oxytocin-neurons by acting on V2-like receptors

The effects of arginine vasopressin (AVP), and of the V2-AVP receptor agonist 1-deamino[8-D-arginine] vasopressin (DDAVP) on release from the vasopressin-neurons and oxytocin-neurons of Long-Evans rats were evaluated using specific radioimmunoassays for rat neurophysins. AVP (1 microgram, 1 nmol) or DDAVP (25 ng, 25 pmol) was administered i.p. to animals 1 h before they received an i.v. infusion of 18% saline at 10 microliters/100 g b. wt./min for 60 min. Both AVP and DDAVP decreased the responsiveness (slope) but not the sensitivity threshold of vasopressin-neurons to acute changes in plasma osmolality. Since the amounts of the peptides giving comparable decreases in responsiveness were directly related to their antidiuretic potencies, it is most probable that this influence is mediated through V2-like receptors. However, while ruling out a significant contribution of V1-type receptors, the data do not exclude involvement of other vasopressin receptors (e.g. V3-type receptors). Both AVP and DDAVP also appeared to have an inhibitory effect on release from oxytocin-neurons, but in this case they significantly altered sensitivity threshold but not responsiveness to acute changes in plasma osmolality. Because AVP produced a shift in sensitivity threshold larger than that by DDAVP when the peptides were used in amounts related to their antidiuretic potencies, our results suggest that the feedback influence of AVP on oxytocin-neurons is largely, although not entirely, exercised through V2-like receptors.     

Anteroventral third ventricle lesions impair cardiovascular responses to intravenous hypertonic saline infusion

The anteroventral third ventricle (AV3V) region is a critical area of the forebrain, acting on fluid and electrolyte balance and maintaining cardiovascular homeostasis. The purpose of this study was to determine the effects of lesions to the anteroventral third ventricle region on cardiovascular responses to intravenous hypertonic saline (HS) infusion. Male Wistar rats were anesthetized with urethane. The femoral artery and jugular vein were cannulated to record mean arterial pressure (MAP) and infuse hypertonic saline (3M NaCl, 0.18 mL/100 g bw, over 1 min), respectively. Renal blood flow (RBF) was recorded by ultrasonic transit-time flow probes. Renal vascular conductance (RVC) was calculated as renal blood flow to mean arterial pressure ratio and expressed as percentage of baseline. After hypertonic saline infusion in sham animals, renal blood flow and renal vascular conductance increased to 137+10% and 125+7% (10 min), and 141+/-10% and 133+/-10% (60 min), respectively. Increases in mean arterial pressure (20-min peak: 12+/-3 mm Hg) were also observed. An acute lesion in the AV3V region (DC, 2 mA 25s) 30 min before infusion abrogated the effects of hypertonic saline. Mean arterial pressure was unchanged and renal blood flow and renal vascular conductance were 107+/-7% and 103+/-6% (10 min), and 107+/-4 and 106+/-4% (60 min), respectively. Marked tachycardia was observed immediately after lesion. Responses of chronic sham or lesioned rats were similar to those of acute animals. However, in chronic lesioned rats, hypertonic saline induced sustained hypertension. These results demonstrate that integrity of the AV3V region is essential for the renal vasodilation that follows acute changes in extracellular fluid compartment composition.     

Facilitatory role of central dopamine in the osmotic release of vasopressin

In conscious rats, intracerebroventricular (i.c.v.) injection of the dopamine antagonist haloperidol (0.15 mumol) blocked increases in plasma vasopressin (AVP) and arterial pressure caused by i.c.v. administration of a hypertonic solution (990 mOsm/kg, 10 microliters), without affecting plasma osmolality, electrolytes or hematocrit. The application of the alpha-adrenergic antagonist phenoxybenzamine (0.15 mumol), however, did not significantly inhibit the responses of plasma AVP and arterial pressure to the hypertonic solution. We concluded that brain dopamine may play a facilitatory role in the osmotically stimulated AVP secretion.     

Cardiovascular responses to microinjection of L-glutamate into the NTS in AV3V-lesioned rats

The excitatory amino acid L-glutamate injected into the nucleus of the solitary tract (NTS) in unanesthetized rats similar to peripheral chemoreceptor activation increases mean arterial pressure (MAP) and reduces heart rate. In this study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the preoptic-periventricular tissue surrounding the anteroventral third ventricle (AV3V region) on the pressor and bradycardic responses induced by injections of L-glutamate into the NTS or peripheral chemoreceptor activation in unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the NTS were used. Differently from the pressor responses (28+/-3 mm Hg) produced by injections into the NTS of sham-lesioned rats, L-glutamate (5 nmol/100 nl) injected into the NTS reduced MAP (-26+/-8 mm Hg) or produced no effect (2+/-7 mm Hg) in acute and chronic AV3V-lesioned rats, respectively. The bradycardia to l-glutamate into the NTS and the cardiovascular responses to chemoreflex activation with intravenous potassium cyanide or to baroreflex activation with intravenous phenylephrine or sodium nitroprusside were not modified by AV3V lesions. The results show that the integrity of the AV3V region is essential for the pressor responses to L-glutamate into the NTS but not for the pressor responses to chemoreflex activation, suggesting dissociation between the central mechanisms involved in these responses.     

Evaluation of the secretory pattern of plasma arginine vasopressin in stroke patients

Arginine vasopressin (AVP) may play a role in the development of ischemic brain edema and/or cerebral vasospasm. Data available on AVP plasma levels in ischemic stroke are few and discordant. In order to ascertain whether changes in AVP plasma levels occur in ischemic stroke, plasma AVP levels, plasma osmolality and mean arterial pressure were determined in 24 patients with unprecedented ischemic cerebral infarction and in 15 controls over a 24-hour period. In stroke patients, mean 24-hour plasma AVP levels (7.2 +/- 0.8 ng/l) were higher (p < 0.05) than in control subjects (2.4 +/- 0.3 ng/l), and correlated with the severity score of the neurologic deficit and the mean size of the lesion. In patients with a more severe neurologic deficit, the mean 24-hour plasma AVP levels (8.7 +/- 1.0 ng/l) were higher than in patients with a less severe neurologic deficit (5.2 +/- 0.8 ng/l). Data indicate that in ischemic stroke an increased AVP secretion occurs independently of osmotic or baroreceptorial mechanisms. The possibility that AVP may play a role in neuronal cell damage following cerebral ischemia warrants further attention.     

Systemic angiotensin II and volume expansion release norepinephrine in the preoptic recess

The periventricular tissue surrounding the anteroventral portion of the third cerebral ventricle (AV3V) of the preoptic recess is critical for several responses evoked by central and peripheral angiotensin II (ang II), and the natriuresis produced by extracellular fluid volume expansion. In addition, several other studies have suggested that the pressor and natriuretic responses evoked by these stimuli are regulated by activation of noradrenergic systems in AV3V tissue. The purpose of the present experiments was to directly determine if i.v. infusion of ang II and volume expansion increase norepinephrine release in the AV3V area using in vivo microdialysis. Male, Sprague-Dawley rats were implanted with microdialysis probes in the AV3V and were tested conscious and unrestrained. Dialysate was collected before, during, and following i.v. administration of ang II or phenylephrine which raised blood pressure 40-50 mmHg, or volume expansion with isotonic saline. Dialysate norepinephrine concentrations from these rats were compared to dialysate norepinephrine content from animals which received no treatment. Both i.v. infusion of ang II and isotonic volume expansion significantly increased dialysate norepinephrine concentration, while infusion of phenylephrine did not alter norepinephrine release in AV3V tissue. These data demonstrate that peripheral ang II and volume expansion selectively increase norepinephrine release in the AV3V region, and are consistent with the conclusion that activation of noradrenergic systems in the AV3V region contribute to cardiovascular and drinking responses evoked by peripheral ang II and to natriuresis following volume expansion.     

Effects of intravenous infusion of substance P on arginine vasopressin and oxytocin secretion in normal men.

In order to establish possible stimulatory effects of increasing plasma concentrations of substance P (SP) on the arginine vasopressin (AVP) and/or oxytocin (OT) secretion, successively increasing doses of SP(0.5, 1 and 1.5 pmol/kg-1/min-1; each dose for 20 min) were infused in 7 normal men. Plasma AVP and OT levels were measured before infusion and every 20 min, just before increasing the infusion dose of SP. During tests, SP infusion did not produce untoward side effects or changes in blood osmolality and/or pressure. Plasma OT levels did not change during SP infusion. Plasma AVP concentrations were not modified by the infusion of the lowest dose of SP, whereas they were significantly increased in a dose response fashion when higher amounts of SP were given. These findings demonstrate for the first time in humans that the systemic administration of SP exerts stimulatory effects on AVP, but not on OT secretion.     

Metabotropic glutamate receptors in the hippocampus and nucleus accumbens are involved in generating seizure-induced hippocampal gamma waves and behavioral hyperactivity

The involvement of metabotropic glutamate receptor (mGluR) subtypes in the generation of hippocampal EEG (30-100 Hz) and behaviors induced by a hippocampal afterdischarge (AD) was examined in freely behaving rats. A hippocampal AD induced an increase in gamma waves (30-100 Hz) for 20 min, accompanied by behavioral hyperactivity. Bilateral intracerebroventricular (i.c.v.) infusion of (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, 30 min before a hippocampal AD, significantly suppressed both the increase in gamma waves and the behavioral hyperactivity. The hippocampal theta rhythm, the spontaneous hippocampal gamma waves, and evoked field potential oscillations of approximately 40 Hz were not affected by MCPG. Pre-infusion (i.c.v.) of (2S)-alpha-ethylglutamic acid (EGLU; a group II mGluR antagonist), but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; a group I mGluR antagonist), suppressed the postictal increase of both hippocampal gamma waves and behaviors. MCPG was infused locally into different brain structures in order to specify its target sites. Intra-hippocampal infusion of MCPG, or EGLU, blocked the increase in both gamma waves and behaviors. Infusion of MCPG into the nucleus accumbens suppressed the postictal behavioral hyperactivity without affecting the increase in hippocampal gamma waves. MCPG injected into the medial septum blocked neither postictal gamma activity nor behavioral hyperactivity. It is suggested that the group II mGluRs in the hippocampus are involved in generation of the postictal hippocampal gamma waves, while behavioral hyperactivity is partly mediated by mGluRs in the nucleus accumbens. However, spontaneous gamma and theta waves in the normal hippocampus are not mediated by mGluRs.     

Intracerebroventricular arginine vasopressin causes intracranial pressure to rise in conscious goats

The effects of intracerebroventricular (i.c.v.) infusion of arginine vasopressin (AVP) on intracranial pressure (ICP), blood pressure (BP) and plasma AVP were investigated in conscious goats. The animals were implanted with ventricular (V) and cisternal (C) cannulae under halothane anaesthesia and allowed to recover prior to experimentation. After 30 min infusion of 20 microliter/min artificial cerebrospinal fluid (CSF) alone, to allow the animals to settle, ICP (estimated at both C and V cannulae), BP and plasma AVP were measured. Then the animals were infused with either artificial CSF alone or 1 or 10 pmol/min AVP for a further 150 min. One pmol/min AVP i.c.v. resulted in significant ICP increases of +2.2 cm CSF (C) and +3.1 cm CSF (V) when compared with artificial CSF alone. Ten pmol/min AVP also led to significant ICP rises of +3.2 cm CSF (C) and +4.2 cm CSF (V). There were no significant changes of BP or plasma AVP during the infusions. We conclude that central infusion of AVP leads to elevated ICP in conscious goats by a mechanism that does not involve BP alteration or changes in plasma AVP.