RESUMO
Changes in blood volume can be caused by different conditions, such as vomiting, diarrhea, alteration of sodium intake, trauma, or the use of diuretics, which can lead to severe health deterioration. Understanding the mechanisms involved in the maintenance of physiological parameters and the hydroelectrolytic balance of the human body during hypovolemia, can help with preventing and handling these high-risk situations. Hence, this study investigated cardiorespiratory [mean arterial pressure (MAP), heart rate (HR), pulmonary ventilation (VE)] and blood parameters, of sodium depleted rats with furosemide and the roles of the central and peripheral renin-angiotensin and the peripheral vasopressinergic systems in controlling blood pressure in these animals. Different groups under the same conditions received subcutaneous (s.c.) injections of furosemide (diuretic/saliuretic) or vehicle, intracerebroventricular (i.c.v.) or intravenous (i.v.) injections of losartan [angiotensin II (ANG II) AT1 receptor antagonist] or saline, and i.v. injections of Manning compound (AVPX, vasopressin V1 receptor antagonist). Sodium depletion increased the VE (708 ± 71, vs. normovolemic: 478 ± 40 mL/min/kg body wt) and did not modify baseline mean arterial pressure (104 ± 4, vs. normovolemic: 105 ± 4 mmHg) and heart rate (334 ± 20, vs. normovolemic: 379 ± 13 bpm). The i.v. losartan (10 mg/kg of body wt) treatment significantly reduced MAP in all groups and elevated HR, with a greater impact in sodium depleted rats before repletion. On the other hand, the i.c.v. losartan (3.3 µg/kg of body wt) and i.v. AVPX (10 µg/kg of body wt) treatments did not alter the MAP and HR in control, sodium depleted, and sodium repleted rats. These results indicate that sodium depletion affects cardiorespiratory control increasing baseline ventilation and peripheral angiotensinergic mechanisms are relevant for maintaining cardiovascular parameters in sodium depleted rats. Besides, this study suggests vasopressin V1 receptors do not participate in the maintenance of MAP and HR in sodium depleted animals with furosemide.
RESUMO
Sodium appetite reverts from aversive to hedonic the orofacial responses to intraoral hypertonic NaCl in a taste reactivity test (TRT). An electrophysiological-based hypothesis suggests that aversion to salty taste results from oral nociception (e.g., like that produced by intraoral capsaicin). In the present work, we used the TRT to investigate whether sodium appetite and its sensitization produce similar effects on the orofacial responses to the intraoral infusion of either capsaicin or hypertonic NaCl. We produced rapid onset sodium appetite by subcutaneous injection of furosemide combined with a low dose of captopril (Furo/Cap) in adult rats instrumented with intraoral cannula. Then, the animals had 1-h free access to water (thirst test). Immediately after, they entered the TRT receiving a first intraoral infusion (1 ml for a total of 1 min) of (0.5 µM) capsaicin and, 20 min later, a second one of (0.3 M) NaCl. The sequence, Furo/Cap injection - thirst test - TRT, was repeated twice more every three days. The repetition of the Furo/Cap increased the frequency of hedonic responses, decreased the frequency of aversive responses, and increased the hedonic:neutral response ratio to NaCl. The repetition of Furo/Cap reduced transiently the neutral orofacial responses and ended decreasing the aversive:neutral response ratio to capsaicin. The results suggest that repeated Furo/Cap sensitizes the palatability of hypertonic NaCl. They also suggest that sensitization of sodium appetite involves increased sodium "liking". Finally yet importantly, we found that sensitization of sodium appetite can influence orofacial responses to capsaicin. Rapid onset sodium appetite and orofacial responses to intraoral capsaicin and hypertonic NaCl in the rat.
Assuntos
Cloreto de Sódio , Sódio , Animais , Apetite , Capsaicina/farmacologia , Furosemida , Humanos , RatosRESUMO
Central cholinergic activation stimulates water intake, but also NaCl intake when the inhibitory mechanisms are blocked with injections of moxonidine (α2 adrenergic/imidazoline agonist) into the lateral parabrachial nucleus (LPBN). In the present study, we investigated the involvement of central M1 and M2 muscarinic receptors on NaCl intake induced by pilocarpine (non-selective muscarinic agonist) intraperitoneally combined with moxonidine into the LPBN or by muscimol (GABAA agonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN and in the lateral ventricle were used. Pirenzepine (M1 muscarinic antagonist, 1 nmol/1 µl) or methoctramine (M2 muscarinic antagonist, 50 nmol/1 µL) injected intracerebroventricularly (i.c.v.) reduced 0.3 M NaCl and water intake in rats treated with pilocarpine (0.1 mg/100 g of body weight) injected intraperitoneally combined with moxonidine (0.5 nmol/0.2 µL) into the LPBN. In rats treated with muscimol (0.5 nmol/0.2 µL) into the LPBN, methoctramine i.c.v. also reduced 0.3 M NaCl and water intake, however, pirenzepine produced no effect. The results suggest that M1 and M2 muscarinic receptors activate central pathways involved in the control of water and sodium intake that are under the influence of the LPBN inhibitory mechanisms.
Assuntos
Ingestão de Líquidos/efeitos dos fármacos , Núcleos Parabraquiais/metabolismo , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M2/metabolismo , Cloreto de Sódio/metabolismo , Animais , Diaminas/farmacologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Imidazóis/farmacologia , Masculino , Agonistas Muscarínicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Muscimol/farmacologia , Núcleos Parabraquiais/efeitos dos fármacos , Pilocarpina/farmacologia , Pirenzepina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor Muscarínico M1/efeitos dos fármacos , Receptor Muscarínico M2/efeitos dos fármacos , Sódio na DietaRESUMO
Peripheral injection of pilocarpine, a cholinergic muscarinic agonist, induces salivation, water intake and hypertension. The medial septal area (MSA) is involved in cardiovascular control and fluid-electrolyte balance. Therefore, the effects of lesions or muscarinic cholinergic blockade in the MSA on the salivation, water intake and pressor responses induced by peripheral pilocarpine (4 micromol/kg of body weight) were investigated. Male Holtzman rats with stainless steel cannulas implanted in the MSA or submitted to electrolytic lesion of MSA were used. MSA lesion (1 day) reduced the salivation (262+/-45 vs. sham: 501+/-30 mg/7 min) and water intake (2.6+/-0.4 vs. sham: 4+/-0.4 ml/1 h) induced by intraperitoneal pilocarpine, whereas 15-day MSA lesion reduced only the pilocarpine-induced water intake (2.3+/-0.5 ml/1 h). Pre-treatment with the muscarinic cholinergic antagonist atropine methyl bromide (4 nmol/0.5 microl) into MSA also reduced the pilocarpine-induced salivation (420+/-33 mg/7 min) and water intake (1.4+/-0.4 ml/1 h). Conversely, MSA lesions or the blockade of muscarinic receptors in the MSA did not change the pressor response induced by intravenous pilocarpine. The results show that MSA and its muscarinic receptors are part of the forebrain circuitry activated by peripheral pilocarpine that induce salivary secretion and water intake. Moreover, they suggest that different central mechanisms are involved in the salivatory, dipsogenic and cardiovascular effects of peripheral pilocarpine in rats.