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Characterization of aldosterone action on hindbrain on the hydroeletrolytic control and cardiovascular regulation

Grant number: 13/00026-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2013
Effective date (End): November 30, 2016
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Eduardo Colombari
Grantee:Silvia Gasparini
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:11/50770-1 - Neural mechanisms involved of hydroelectrolytic balance and cardiorespiratory control, AP.TEM
Associated scholarship(s):15/03290-5 - Angiotensinergic mechanisms involved in sodium intake induced by aldosterone infusion into 4th ventricle, BE.EP.PD

Abstract

Recent results have shown that aldosterone infused into the 4thV produces intense sodium intake, but it is not known if these responses are the result of a direct activation of mechanisms involved in sodium intake or an indirect activation, such as sodium excretion. In this project, we propose to investigate: 1) whether aldosterone infused into the 4thV produces changes in renal excretion of water and electrolytes, blood pressure, heart rate and cardiovascular reflexes, 2) the activation of central areas and HSD2 neurons in the NTS after aldosterone infusion in the 4thV; 3) the synergism between infused aldosterone in the 4thV and ANG II acting in prosencephalic areas on water and NaCl 1.8% intake; 4) the LPBN participation on 1.8% NaCl intake induced by bolus injection or chronic infusion of aldosterone in the 4thV or VL through bilateral injections of moxonidine (±2 adrenergic agonist / imidazole) of methysergide (serotinergic antagonist) or DOI (serotoninergic agonist). In control rats or in animals with reduced expression of mineralocorticoid receptors (MR) done through adenovirus injection, stainless steel guide-cannulas will be implanted in the 4thV and chronic infusion of aldosterone (100 ng/2 µl/h) will be done. Water and 1.8% NaCl intake, urinary excretion of water and electrolytes will be measured daily and on the seventh day after startingthe infusion, blood pressure and heart rate will be recorded in unanesthetized animals through the femoral arterycannulation. The activity of brain areas and HSD2 neurons in the NTS will be studied using the detection of c-fos protein by immunohistochemistry. In this project will also be used animals with stainless steel guide-cannulas implanted in the 4thV and VL, where it will be injected aldosterone (10 ng/2 µl/h) and ANG II (50 ng/ul) or losartan (100 mg/1 µl), respectively in order to study the synergism between aldosterone and angiotensin II on water and 1.8% NaCl intake. Finally, to check the involvement of LPBN in 1.8% NaCl intake induced by aldosterone, rats with stainless steel guide-cannulas implanted in LPBN and 4thV or VL will be used. These animals will receive acute injections of methysergide (4 µg/0.2 µl) or moxonidine (0.5 nmol/0.2 µl) into the LPBN combined with injection of aldosterone in the 4thV or VL. Water and 1.8% NaClintake will alsobe measured in animals with chronic infusion of aldosterone (10 ng/2 µl /h) and bilateral injections of DOI (5 µg/0.2 µl), aserotinergicantagonist, in LPBN.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GASPARINI, S.; MELO, M. R.; NASCIMENTO, P. A.; ANDRADE-FRANZE, G. M. F.; ANTUNES-RODRIGUES, J.; YOSTEN, G. L. C.; MENANI, J. V.; SAMSON, W. K.; COLOMBARI, E. Interaction of central angiotensin II and aldosterone on sodium intake and blood pressure. Brain Research, v. 1720, OCT 1 2019. Web of Science Citations: 1.
GASPARINI, S.; MELO, M. R.; ANDRADE-FRANZE, G. M. F.; GEERLING, J. C.; MENANI, J. V.; COLOMBARI, E. Aldosterone infusion into the 4th ventricle produces sodium appetite with baroreflex attenuation independent of renal or blood pressure changes. Brain Research, v. 1698, p. 70-80, NOV 1 2018. Web of Science Citations: 1.
GASPARINI, S.; MELO, M. R.; LEITE, G. F.; NASCIMENTO, P. A.; ANDRADE-FRANZE, G. M. F.; MENANI, J. V.; COLOMBARI, E. RAPID STIMULATION OF SODIUM INTAKE COMBINING ALDOSTERONE INTO THE 4TH VENTRICLE AND THE BLOCKADE OF THE LATERAL PARABRACHIAL NUCLEUS. Neuroscience, v. 346, p. 94-101, MAR 27 2017. Web of Science Citations: 1.

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