Functional relationship between subfrnical organ cholinergic stimulation and nitrergic activation influencing cardiovascular and body fluid homeostasis

We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel carmula were implanted into their SFO. The volume of injection was 0.2 mu l. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 mu g), L-NAME (40 mu g) and LAR (30 mu g) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 mu g) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis. (c) 2007 Elsevier B.V All rights reserved.

ROLE OF LATERAL HYPOTHALAMUS ON FLUID, ELECTROLYTE, AND CARDIOVASCULAR-RESPONSES TO ACTIVATION OF THE MSA

In this study we investigated the influence of electrolytic lesion or of opioid agonist injections into the lateral hypothalamus (LH) on the dipsogenic, natriuretic, kaliuretic, antidiuretic, presser, and bradycardic effects of cholinergic stimulation of the medial septal area (MSA) in rats. Sham- and LH-lesioned male Holtzman rats received a stainless steel cannula implanted into the LH. Other groups of rats had cannulas implanted simultaneously into the MSA and LH. Carbachol (2 nmol) injection into the MSA induced water intake, presser, and bradycardic responses. LH lesion reduced all of these effects (1-3 and 15-18 days). Previous injection of synthetic opiate agonist, FK-33824 (100 ng), into the LH reduced the water intake, natriuresis, kaliuresis, and presser responses induced by carbachol injected into the MSA. These data show that both electrolytic lesion or injection of an opiate agonist in the LH reduces the fluid-electrolyte and cardiovascular responses to cholinergic activation of the MSA. The involvement of LH with central excitatory and inhibitory mechanisms related to fluid-electrolytic and cardiovascular control is suggested.

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.

Synergist interaction between angiotensin II and DOCA on sodium and water balance in rats

Blockade of central angiotensin receptors with the specific antagonist [Leu8]-ANG II abolished water ingestion and water and sodium excretion induced by infusion of angiotensin II (ANGII) into the lateral ventricle (LV) of rats. The antagonist reduced but did not suppress the salt appetite induced by ANGII infusion. Subcutaneous injection of deoxycorticosterone acetate (DOCA) caused increases in water and 3% NaCl ingestion and decreases in sodium excretion. When central ANGII infusion was combined with peripheral DOCA, the water intake was similar to that induced by ANGII alone and the ingestion of 3% NaCl was increased, whereas sodium excretion was inhibited. When ANGII was infused alone, a detailed temporal analysis of fluid and sodium balance showed a negative balance similar those saline controls that persisted throughout the experiment. Combined administration of ANGII and DOCA induce significant changes in water and sodium balance. Sodium and water maintained a positive balance through out the 8-h experiment. The data support an interaction of central ANGII and DOCA on sodium intake and water and sodium balance. © 1994.

Role of the medial septal area on the cardiovascular, fluid and electrolytic responses to angiotensin II and cholinergic activation into the subfornical organ in rats

In the present study we investigated the effect of electrolytic lesion of the medial septal area (MSA) on the pressor and dipsogenic response to cholinergic activation and angiotensin II (ANGII) injection into the subfornical organ (SFO) in rats. In addition the effect of MSA lesion on the natriuresis, kaliuresis and diuresis after cholinergic activation of the SFO was also investigated. Sham- and MSA-lesioned rats with a stainless steel cannula implanted into the SFO was used. The injection of ANGII (12 ng) into the SFO in sham rats produced pressor (24 ± 2 mmHg) and dipsogenic (9.6 ± 1.1 ml/h) responses. MSA lesion, both acute (2-6 days) and chronic (15-19 days), reduced the pressor (14 ± 2 mmHg) and dipsogenic (2.7 ± 1 ml/h) responses to ANGII into SFO. The injection of the cholinergic agonist carbachol (2 nmol) into the SFO in sham rats produced pressor (48 ± 4 mmHg), dipsogenic (10 ± 1.2 ml/h), natriuretic (457 ± 58 μEq/2 h) and kaliuretic (249 ± 16 μEq/2 h) responses. Acute, but not chronic MSA lesion reduced the pressor (27 ± 3 mmHg), natriuretic (198 ± 55 μEq/2 h) and kaliuretic (128 ± 16 μEq/2 h) responses to carbachol into SFO. No change in the dipsogenic response to carbachol into the SFO was observed in MSA-lesioned rats. Antidiuresis after carbachol was observed only in MSA-lesioned rats. The present results show that the MSA plays a role on the pressor, natriuretic and kaliuretic responses to cholinergic activation of the SFO in rats and on the pressor and dipsogenic responses to ANGII into the same area. In addition, they provide circumstancial evidence for separate circuits subserving the dipsogenic response to central cholinergic and angiotensinergic activation. A facilited diuresis after MSA lesion is also suggested.

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.

Opiate activation suppresses the drinking, pressor and natriuretic responses induced by cholinergic stimulation of the medial septal area

The present study investigates the participation and interaction between cholinergic and opiate receptors of the medial septal area (MSA) in the regulation of Na+, K+ and water excretion, drinking and blood pressure regulation. Male Holtzman rats were implanted with stainless steel cannulae opening into the MSA. Na+, K+ and water excretion, water intake and blood pressure were measured after injection of carbachol (cholinergic agonist), FK-33824 (an opiate agonist) + carbachol or naloxone (an opiate antagonist) + carbachol into MSA. Carbachol (0.5 or 2.0 nmol) induced an increase in Na+ and K+ excretion, water intake and blood pressure and reduced the urinary volume. FK-33824 reduced the urinary volume and Na+ and K+ excretion. Previous injection of FK-33824 (100 ng) into the MSA blocked the increases in Na+ and K+ excretion, water intake and blood pressure induced by carbachol. Naloxone (10 μg) produced no changes in the effect of 2.0 nmol carbachol, but potentiated the natriuretic effect induced by 0.5 nmol dose of carbachol. These data show an inhibitory effect of opiate receptors on the changes in cardiovascular, fluid and electrolyte balance induced by cholinergic stimulation of the MSA in rats. © 1992.

Preoptic-periventricular tissue (AV3V): central cholinergic-induced hydromineral and cardiovascular responses, and salt intake.

The periventricular tissue of the anterior ventral portion of the third ventricle (AV3V) is an important area for the control of hydromineral balance and of cardiovascular function. The present work discusses the importance of the integrity of the AV3V for multiple responses to central cholinergic activation (water intake, hypertension, natriuresis, salivation) and for the control of salt intake.

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.

Nitrergic pathways and L-type calcium channel of MnPO influencing cardiovascular homeostasis

The median preoptic nucleus (MnPO) is one of most important site of the lamina terminalis implicated in the regulation of hydro electrolytic and cardiovascular balance. The purpose of this study was to determine the effect of L-Type calcium channel antagonist, nifedipine, on the increase of median arterial blood pressure (MAP) induce by angiotensin II (ANG II) injected into the MnPO. The influence of nitric oxide (NO) on nifedipine antipressor action has also been studied by utilizing N W-nitro-L-arginine methyl ester (L-NAME) (40 μg 0.2 μL -1) a NO synthase inhibitor (NOSI), 7-nitroindazole (7-NIT) (40 μg 0.2 μL -1), a specific neuronal NO synthase inhibitor (nNOSI) and sodium nitroprusside (SNP) (20 μg 0.2 μL -1) a NO donor agent. We have also investigated the central role of losartan and PD123349 (20 nmol 0.2 μL -1), AT 1 and AT 2, respectively (selective non peptide ANG II receptor antagonists), in the pressor effect of ANG II (25 pmol 0.2 μL -1) injected into the MnPO. Male Wistar rats weighting 200-250 g, with cannulae implanted into the MnPO were utilized. Losartan injected into the MnPO, prior to ANG II, blocked the pressor effect of ANGII. PD 123319 only decreased the pressor effect of ANG II. Rats pre-treated with either 50 μg 0.2 μL -1 or 100 μg 0.2 μL -1 of nifedipine, followed by 25 pmol 0.2 μL -1 of ANG II, decreased ANG II-pressor effect. L-NAME potentiated the pressor effect of ANG II. 7-NIT injected prior to ANG II into the MnPO also potentiated the pressor effect of ANGII but with less intensity than that of L-NAME. SNP injected prior to ANG II blocked the pressor effect of ANG II. The potentiation action of L-NAME and 7-NIT on ANG II-pressor effect was blocked by prior injection of nifedipine. The results described in this study provide evidence that calcium channels play important roles in central ANG II-induced pressor effect. The structures containing NO in the brain, such as MnPO, include both endothelial and neuronal cells, which might be responsible for the influence of nifedipine on the pressor effect of ANG II. These data have shown the functional relationship between L-Type calcium channel and a free radical gas NO in the MnPO, on the control of ANG II-induced pressor effect acting in AT 1 and AT 2 receptors.

Associations between bioelectrical impedance parameters and cardiovascular events in chronic dialysis patients

Purpose: Malnutrition and fluid overload contribute to the poor cardiovascular prognosis of dialysis patients. Since bioelectrical impedance analysis is an option for the evaluation of body composition and for the monitoring of hydration state, it may assist in the identification of subjects at high cardiovascular risk. The objective of this study was to evaluate the association between bioelectrical impedance parameters and cardiovascular events. Methods: The association between bioelectrical impedance parameters and fatal and non-fatal cardiovascular outcome was evaluated in 145 dialysis patients. Results: The mean age of the population studied was 54.9 ± 15.4 years, 49.7 % were males, and 35.9 % had diabetes. Forty (27.6 %) patients developed cardiovascular events during the 16 months (8; 32) of follow-up. Comparison of patients with and without cardiovascular events revealed higher extracellular mass/body cell mass (ECM/BCM) and extracellular water/total body water ratios and higher C-reactive protein levels in the former. Survival analysis showed that an ECM/BCM ratio >1.2 and a phase angle <6° were associated with poor cardiovascular prognosis. Among nondiabetic patients, these parameters and capacitance were independently associated with cardiovascular events, suggesting that poor nutritional status and fluid overload are associated with the occurrence of these events. Conclusions: Phase angle, capacitance and ECM/BCM ratio are valuable parameters for the evaluation of cardiovascular prognosis, supporting the use of bioelectrical impedance for the clinical assessment of dialysis patients. © 2012 Springer Science+Business Media Dordrecht.

Control of respiratory and cardiovascular functions by leptin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Renal and cardiovascular effects of Bothrops marajoensis venom and phospholipase A(2)

Bothrops marajoensis is found in the savannah of Marajo Island in the State of Par S and regions of Amapa State, Brazil. The aim of the work was to study the renal and cardiovascular effects of the B. marajoensis venom and phospholipase A(2) (PLA(2)). The venom was fractionated by Protein Pack 5PW. N-terminal amino acid sequencing of sPLA(2) showed amino acid identity with other lysine K49sPLA(2)s of snake venom. B. marajoensis venom (30 mu g/mL) decreased the perfusion pressure, renal vascular resistance, urinary flow, glomerular filtration rate and sodium tubular transport. PLA(2) did not change the renal parameters. The perfusion pressure of the mesenteric bed did not change after infusion of venom. In isolated heart, the venom decreased the force of contraction and increased PP but did not change coronary flow. In the arterial pressure, the venom and PLA(2) decreased mean arterial pressure and cardiac frequency. The presence of atrial flutter and late hyperpolarisation reversed, indicating QRS complex arrhythmia and dysfunction in atrial conduction. In conclusion, B. marajoensis venom and PLA(2) induce hypotension and bradycardia while simultaneously blocking electrical conduction in the heart. Moreover, the decrease in glomerular filtration rate, urinary flow and electrolyte transport demonstrates physiological changes to the renal system. (C) 2009 Elsevier Ltd. All rights reserved.

Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)