Influence of arginine vasopressin receptor and nitric oxide on the water, sodium intake and arterial blood pressure induce by angiotensin injected into third ventricle of the brain

As several structures of the central nervous system are involved in the control of hydromineral and cardiovascular balance we investigated whether the natriorhexigenic and pressor response induced by the injection of ANG II into the 3rd V could be mediated by vasopressinergic and nitrergic system. Male Holtzman rats weighing 200-250 g with cannulae implanted into the 3rd V were used. The drugs were injected in 0.5 μL over 30-60 sec. Controls were injected with a similar volume of 0.15 M NaCl. ANGII increased the water intake vs control. AVPA injected into 3rd V prior to ANGII decreased the dipsogenic effect of ANGII. L-arginine also decreased the water intake induced by ANGII. AVPA plus L-arginine inhibit the water intake induced by ANGII. 7NIT injected prior to ANGII potentiated the dipsogenic effect of ANGII. Pre-treatment with ANGII increased the sodium ingestion vs control. AVPA decreased the ANGII effect in sodium intake. L-arginine also decreased the natriorhexigenic effect of ANGII. The combination of L-arginine and AVPA inhibit the sodium intake induced by ANGII. 7NIT injected prior to ANGII potentiated the sodium intake induced by ANGII. ANGII induced an increase in Mean Arterial Pressure (MAP) vs control. AVPA and L-arginine induced a decreased in the pressor effect of ANGII. The combination of L-arginine and AVPA inhibit the pressor effect of ANGII. 7NIT injected prior to ANGII into 3rd V potentiated the pressor effect of ANGII. These data suggest that arginine vasopressin V 1 receptors and Nitric Oxide (NO) within the circumventricular structures may be involved in sodium intake and pressor response induced by the activation of ANGII receptors within the circumventricular neurons. These studies revealed the involvement of sodium appetite by utilizing the angiotensinergic, vasopressinergic and nitrergic system in the central regulation of blood pressure. © 2006 Asian Network for Scientific Information.

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1 mu l and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, 0.15 M NaCl) into the 3rdV, water ingestion was 0.3 +/- 0.1 ml/h. Ramipril (1 mu g/mu l) injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 +/- 0.2 ml/h). The injection of noradrenaline (40 nmol/mu l) after isotonic saline induced an increase in water intake (3.0 +/- 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 +/- 0.3 ml/h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.

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. (C) 2004 Elsevier B.V. All rights reserved.

Effect of AV3V lesion on the cardiovascular, fluid, and electrolytic changes induced by activation of the lateral preoptic area

In this study we investigated the effect of the anteroventral third ventricle (AV3V) lesion on the pressor, bradycardic, natriuretic, kaliuretic, and dipsogenic responses induced by the injection of the cholinergic agonist carbachol into the lateral preoptic area (LPOA) in rats. Male Holtzman rats with sham or electrolytic AV3V lesion were implanted with stainless steel cannula directly into the LPOA. Injection of carbachol (7.5 nmol) into the LPOA of sham rats induced natriuresis (405 ± 66 μEq/120 min), kaliuresis (234 ± 44 μEq/120 min), water intake (9.5 ± 1.7 ml/60 min), bradycardia (-47 ± 11 bpm), and increase in mean arterial pressure (28 ± 3 mmHg). Acute AV3V lesion (1-5 days) reduced the natriuresis (12 ± 4 μEq/120 min), kaliuresis (128 ± 27 μEq/120 min), water intake (1.7 ± 0.9 ml/60 min), and pressor responses (14 ± 4 mmHg) produced by carbachol into the LPOA. Tachycardia instead of bradycardia was also observed. Chronic (14-18 days) AV3V lesion reduced only the pressor response (10 ± 2 mmHg) induced by carbachol. These results showed that acute, but not chronic, AV3V lesion reduced the natriuretic, kaliuretic, and dipsogenic responses to carbachol injection into the LPOA. The pressor response was reduced in acute or chronic AV3V-lesioned rats. The results suggest that the lateral areas may control the fluid and electrolyte balance independently from the AV3V region in chronic AV3V-lesioned rats. © 1992.

Importância da região anteroventral do terceiro ventrículo (AV3V) no controle cardiovascular e do equilíbrio hidroeletrolítico

The maintenance of the arterial pressure in normal levels is important for the homeostasis of body fluids. The central nervous system regulating sympathetic and parasympathetic autonomic efferent can adjust arterial pressure which allows animals or human to face different daily activities with the best performance. Different central areas are responsible for the control of autonomic discharges to cardiovascular system and many of them are also involved in the control of fluid electrolyte balance. One of these areas is the tissue surrounding the anteroventral third ventricle (AV3V region) localized in the forebrain and a main central site for angiotensin II receptors and osmoreceptors. The AV3V lesions impair the development of many models of experimental hypertension in rats and the pressor responses to different stimuli. Lesions of the AV3V region also reduce dipsogenic responses to angiotensin II, central cholinergic activation, water deprivation and increase in plasma osmolarity, atrial natriuretic peptide secretion produced by body fluid expansion and the increase in renal excretion to central cholinergic activation. Recent evidence also suggests the participation of AV3V region in pressor responses produced by the activation of medullary mechanisms.

LESION OF THE ANTEROVENTRAL 3RD VENTRICLE REGION IMPAIRS THE RECOVERY OF ARTERIAL-PRESSURE INDUCED BY HYPERTONIC SALINE IN RATS SUBMITTED TO HEMORRHAGIC-SHOCK

The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arteria pressure (MAP) after hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion of the anteroventral third ventricle (AV3V) region (4 h, 4 and 20 days). Rats anesthetized with thiopental sodium were bled (about 2.8 ml/100 g) until the MAP was stabilized at the level of 60 mmHg for 30 min. In sham-lesioned rats, MAP increased to 90 mmHg and became stable near this level after intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.). In AV3V-lesioned rats, the same infusion induced a smaller increase in MAP (80 mmHg) and the MAP returned to pre-infusion levels within 30 min. These results show that the AV3V region plays an important role in the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.

Brain versus peripheral angiotensin II receptors in hypovolaemia: Behavioural and cardiovascular implications

1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure, Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain.2. Conflicting data have been reported for the role of systemic versus brain AngII in the mediation of sodium appetite.3. The role for systemic AngII and systemic AngII receptors in the control of blood pressure in hypovolaemia is well established. In contrast with systemic injections, i.c.v injections of AngII non-peptide AT(1) and AT(2) receptor antagonists, such as losartan and PD123319, do not reduce arterial pressure in sodium-depleted (furosemide injection plus removal of ambient sodium for 24 h) rats. Thus, brain AngII receptors are likely not important for cardiovascular responses to hypovolaemia induced by sodium depletion.4. Intracerebroventricular injections of losartan or PD 123319 increase arterial pressure when injected at relatively high doses. This hypertensive effect is unlikely to be an agonist effect on brain AngII receptors, Increases in arterial pressure produced by i.c.v, losartan are attenuated by lesions of the tissue surrounding the anterior third ventricle (AV3V). The hypertensive effect of i.c.v, AngII is abolished by lesions of the AV3V.5. Hypertension induced by AngII receptor antagonists is consistent with hypotension induced by AngII acting in the brain, However, the full physiological significance of this hypotensive effect mediated by brain AngII receptors remains to be determined.

Different effects on rat arterial pressure and heart rate when losartan is injected into the third or fourth ventricle

Cardiovascular responses to central losartan (LOS), a non-peptide angiotensin II (ANG II) receptor antagonist, were investigated by comparing the effects of LOS injection into the 3rd and 4th cerebral ventricles (3rdV, 4thV) on mean arterial pressure (MAP) and heart rate (HR). Adult male Holtzman rats were used (N=6 animals per group). Average basal MAP and HR were 114±3 mmHg and 343±9 bpm (N=23), respectively. LOS (50, 100 or 200 nmol/2 μl) injected into the 3rdV induced pressor (peak of 25±3 mmHg) and tachycardic (peak of 60±25 bpm) responses. LOS injected into the 4thV had no effect on MAP, but it induced bradycardia (peak of -35±15 bpm). KCl (200 nmol/2 μl) injected into the 3rdV or into the 4thV had no effect on either MAP or HR compared to 0.9% saline injection. The results indicate that LOS injected into the third ventricle acts on forebrain structures to induce its pressor and tachycardic effects and that bradycardia, likely dependent on hindbrain structures, is obtained when LOS is injected into the fourth ventricle.

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 (I 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 turn 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. (C) 2004 Elsevier B.V. All rights reserved.

Effects of AV3V lesion on pilocarpine-induced pressor response and salivary gland vasodilation

The cholinergic agonist pilocarpine injected intraperitoneally (ip) increases mean arterial pressure (MAP) and superior mesenteric (SM) vascular resistance and reduces submandibular/sublingual gland (SSG) vascular resistance. In the present study, we investigated the effects of electrolytic lesions of the anteroventral third ventricle (AV3V) region on the changes in MAP, SM, and SSG vascular resistances induced by ip pilocarpine. Male Holtzman rats anesthetized with urethane (1.0 g/kg) and chloralose (60 mg/kg) were submitted to sham or electrolytic AV3V lesions and bad pulsed Doppler flow probes implanted around the arteries. Contrary to sham rats, in 1-h and 2-day AV3V-lesioned rats, pilocarpine (4 mu mol/kg) ip decreased MAP (-41 +/- 4 and -26 4 mm Hg, respectively, vs. sham: 19 +/- 4 mm Hg) and SM (-48 +/- 11 and -45 +/- 10%, respectively, vs. sham: 41 +/- 10%) and hindlimb vascular resistances (-65 +/- 32 and -113 +/- 29%, respectively, vs. sham: 19 +/- 29%). In 7-day AV3V-lesioned rats, pilocarpine produced no changes on MAP and SM and hindlimb vascular resistances. Similar to sham rats, pilocarpine reduced SSG vascular resistance 1 h after AV3V lesions (-46 +/- 6%, vs. sham: -40 +/- 6%), but it produced no effect 2 days after AV3V lesions and increased SSG vascular resistance (37 6%) in 7-day AV3V-lesioned rats. The responses to ip pilocarpine were similar in 15-day sham and AV3V-lesioned rats. The cholinergic antagonist atropine methyl bromide (10 nmol) iv slightly increased the pressor response to ip pilocarpine in sham rats and abolished for 40 min the fall in MAP induced by ip pilocarpine in 1-h AV3V-lesioned rats. The results suggest that central mechanisms dependent on the AV3V region are involved in the pressor responses to ip pilocarpine. Although it was impaired 2 and 7 days after AV3V lesions, pilocarpine-induced salivary gland vasodilation was not altered 1 h after AV3V lesions which suggests that this vasodilation is not directly dependent on the AV3V region. (c) 2005 Elsevier B.V. All rights reserved.

AV3V lesions reduce the pressor response to L-glutamate into the RVLM

Neurons from the rostral ventrolateral medulla (RVLM) directly activate sympathetic preganglionic neurons in the spinal cord. Hypertensive responses and sympathetic activation produced by different stimuli are strongly affected by lesions of the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V region). Therefore, in the present study, we investigated the effects of acute (1 day) and chronic (IS days) electrolytic lesions of the AV3V region on the pressor responses produced by injections of the excitatory amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula. implanted into the RVLM were used. The pressor responses produced by injections of L-glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39 +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6, 39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2 and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in sham or AV3V-lesioned rats produced no significant change in the heart rate (HR). Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium nitroprusside, respectively, and the pressor and bradycardic responses to chemoreflex activation with iv potassium cyanide were not modified by AV3V lesions. The results suggest that signals from the AV3V region are important for sympathetic activation induced by L-glutamate into the RVLM. (c) 2006 Elsevier B.V. All rights reserved.

Central cholinergic blockade reduces the pressor response to L-glutamate into the rostral ventrolateral medullary pressor area

Injections of the excitatory amino acid L-glutamate (L-glu) into the rostral ventrolateral medulla (RVLM) directly activate the sympathetic nervous system and increase mean arterial pressure (MAP). A previous study showed that lesions of the anteroventral third ventricle region in the forebrain reduced the pressor response to L-glu into the RVLM. In the present study we investigated the effects produced by injections of atropine (cholinergic antagonist) into the lateral ventricle (LV) on the pressor responses produced by L-ghl into the RVLM. Male Holtzman rats (280-320 g, n=5 to 12/group) with stainless steel cannulas implanted into the RVLM, LV or 4th ventricle (4th V) were used. MAP and heart rate (HR) were recorded in unanesthetized rats. After saline into the LV, injections of L-glu (5 nmol/100 nl) into the RVLM increased MAP (51 +/- 4 mm Hg) without changes in HR. Atropine (4 nmol/1 PI) injected into the LV reduced the pressor responses to L-glu into the RVLM (36 +/- 5 mm Hg), However, atropine at the same dose into the 4th V or directly into the RVLM did not modify the pressor responses to L-glu into the RVLM (45 +/- 2 and 49 +/- 4 mm Hg, respectively, vs. control: 50 +/- 4mmHg). Central cholinergic blockade did not affect baro and chemoreflex nor the basal MAP and HR. The results suggest that cholinergic mechanisms probably from forebrain facilitate or modulate the pressor responses to L-glu into the RVLM. The mechanism is activated by acetylcholine in the forebrain, however, the neurotransmitter released in the RVLM to facilitate the effects of glutamate is not acetylcholine. (C) 2007 Elsevier B.V. All rights reserved.