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Possible interaction between Angiotensin II and aldosterone in renovascular hypertension in Wistar rats

Grant number: 13/13332-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2014
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Ruy Ribeiro de Campos Junior
Grantee:Gisele Silvério Lincevicius
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:09/54225-8 - The pathophysiology of congestive heart failure: from the organ to tile molecules, AP.TEM
Associated scholarship(s):15/21065-9 - Renal and CHEMORRECEPTOR afferents in the control of sympathetic VASOTOMOTOR tone in renovascular hypertension, BE.EP.DR

Abstract

It is well established that the renin-angiotensin-aldosterone-system (RAAS) plays an important role in the generation and maintenance of renovascular hypertension. The major effectors of the RAAS are angiotensin II (Ang II) and aldosterone (Aldo) acting on specific receptors promoting increase in blood pressure (BP) and consequential effects on blood vessels, heart, kidneys and central nervous system (CNS). Recently, has been shown that Ang II and Aldo can act synergistically via AT1 and MR receptors, respectively. Previous studies demonstrated that a subpressor preconditioning dose of Ang II or Aldo potentiate the hypertensinogenic effects of Ang II. Based on this evidences and our previous results, our hypothesis is that the mechanisms of cardiovascular regulation of two kidneys - one clip (2K-1C) are sensitized by action of Ang II. Therefore the aim of the present study is to evaluate the chronic interaction between Ang II and Aldo on autonomic and cardiovascular regulation in 2K-1C model. The effects of previous MR receptors blockade (Spironolactone administration) and after a break period (7 days) a subsequent AT1 receptor blockade (Losartan administration) will be evaluated, in the same way we will test the effects of reverse treatment. The effects on BP, postganglionic sympathetic nervous activation to different territories (renal and lumbar) and sensitivity of arterial baroreceptors by renal and lumbar territories in 2K-1C animals will be investigated. After that, we will evaluate in treated and untreated groups, the presence of HSD2 neurons in intermediate nucleus of tractus solitarius (NTS), paraventricular hypothalamic nuclei (PVN) and the rostral ventrolateral medulla (RVLM). Additionally, we will verify if a neuron of PVN and RVL coexpress the hydroxylase tyrosine enzyme (TH) and the 11²-HSD2 enzyme. Finally, using western blotting (WB) and real-time PCR, we will test if chronic treatments in 2K-1C animals modify the protein and gene expression of AT1 receptors in intermediate NTS, RVLM and PVN. We will also evaluate in these central areas the protein expression of MR receptors, glucocorticoid-regulated kinase protein (Sgk1 - which is a marker of MR activity), 11²-HSD2 enzyme, angiotensinogen and angiotensin-converting enzyme by WB. With this project we intend to further our understanding regarding the mechanism of interaction between Ang II e Aldo in the cardiovascular control in the renovascular hypertension. (AU)

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)
MILANEZ, MAYCON I. O.; NISHI, ERIKA E.; SATO, ALEX Y. S.; FUTURO NETO, HENRIQUE A.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R. Control of renal sympathetic nerve activity by neurotransmitters in the spinal cord in Goldblatt hypertension. Brain Research, v. 1698, p. 43-53, NOV 1 2018. Web of Science Citations: 0.
LINCEVICIUS, GISELE S.; SHIMOURA, CAROLINE G.; NISHI, ERIKA E.; OLIVEIRA, TALES; CESPEDES, JULIANA G.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R. Differential effects of renal denervation on arterial baroreceptor function in Goldblatt hypertension model. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 208, p. 43-50, DEC 2017. Web of Science Citations: 2.

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