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Central mechanisms involved in the control of arterial pressure and water and sodium intake


Important inhibitory mechanisms for the control of sodium and water intake are present in the lateral parabrachial nucleus (LPBN). Serotonergic, cholecystokinergic and glutamatergic mechanisms and the corticotropin releasing hormone (CRF) in the LPBN inhibit water and sodium intake, whereas gabaergic, opioid and alpha2 adrenergic mechanisms in the LPBN have opposite effects. Besides the control of water and sodium intake, the LPBN is also involved in the control of renal excretion and cardiovascular responses. Recent results from our laboratory have shown that noradrenaline acting on alpha2 adrenoceptors in the LPBN produces a strong increase in the intake of 0.3M NaCl induced by the treatment with the diuretic furosemide (FURO) combined with low dose of the angiotensin converting enzyme inhibitor captopril (CAP) injected subcutaneously (sc). Injections of noradrenaline into the LPBN also produce strong pressor responses. Therefore, one of the proposal in the present project is to investigate: 1) the subtypes of adrenergic receptors in the LPBN and the peripheral mechanisms (sympathetic and/or vasopressin release) involved in the cardiovascular responses to noradrenaline into the LPBN; 2) if the alpha1 adrenoceptors in the LPBN were also involved in the control of water and 0.3 M NaCl intake produced by the treatment with FURO+CAP; 3) possible changes on renal excretion produced by injections of noradrenaline into the LPBN. Other results from our laboratory have shown that electrolytic lesions or the blockade of the neurons in the central nucleus of the amygdala (CeA) by the injection of the gabaergic agonist muscimol abolished the increase of water and sodium intake produced by the blockade of the inhibitory mechanisms of the LPBN, suggesting that these two areas interacts each other. Therefore, a proposal of this project is also to investigate possible inhibitory (gabaergic) or facilitatory (angiotensinergic or mineralocorticoids) mechanisms of the CeA involved in the control of water and sodium intake and if these mechanisms would be affected by LPBN inhibitory mechanisms. Bilateral injections of the non-specific opioid agonist beta-endorphin into the LPBN also increases water and sodium intake. Then, another purpose of the present project is to investigate possible role mu opioid receptors in the LPBN in the control of water and 0.3 M NaCl intake induced by FURO + CAP treatment, by testing the effects of the specific mu opioid agonist endomorphin and the ¼ opioid antagonist CTAP alone or combined into the LPBN. It was also recently shown that the ingestion of water and 0.3M NaCl by normovolemic and satiated rats treated with muscimol into the LPBN is strongly reduced by central cholinergic or angiotensinergic blockade with injections of atropine or losartan, respectively, into the lateral ventricle (LV). This unexpected and apparently paradoxical involvement of central cholinergic mechanisms on water and especially sodium intake has raised many questions and one is whether central cholinergic mechanisms would be important for sodium intake that arises after the blockade of the LPBN inhibitory mechanism in other conditions. Therefore, another purpose of the present project is to investigate the participation of central cholinergic and angiotensinergic mechanisms in the increase of water and 0.3M NaCl produced by bilateral injections of moxonidine (alpha2 adrenergic/imidazoline agonist) into the LPBN in rats treated with intragastric load with 2 M NaCl (2 ml/rat) or in rats treated with FURO+CAP sc. Male rats with stainless steel cannulas implanted bilaterally into the LPBN (and into the CeA or LV) will be used and central injections in a volume of 0.2 or 1 ul will be done using a 5 ul Hamilton syringe. Arterial pressure and heart rate will be recorded in conscious normotensive rats that have femoral artery cannulated in the day before tests. Water and 0.3M NaCl intake will be recorded for 2 to 4 h after central injection. (AU)

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