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Role of the aldosterone in oxidative stress and sympathetic activity in renovascular hypertension in Wistar rats

Grant number: 10/04333-6
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): August 01, 2010
Effective date (End): July 31, 2012
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Ruy Ribeiro de Campos Junior
Grantee:Gisele Silvério Lincevicius
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


The renin-angiotensin-aldosterone system plays an important role in the genesis and maintenance of arterial renovascular hypertension. The main mechanism of this system may be attributed to the effects caused by increased angiotensin II (Ang II), such as vasoconstrictor effects, maintenance of sympathetic hyperactivity, as well as the NAD(P)H oxidase activation via interaction with AT1 receptors resulting in oxidative stress. Several studies focuses on the Ang II as the main mechanism leading to increased oxidative stress. However, it is unclear how the mechanisms are involved in the regulation of renin-angiotensin system (RAS) in these pathophysiological conditions, for example, as previously shown, aldosterone may activate the NAD(P)H oxidase independent of AT1 receptors in normal animals. So far there is no information on the role of aldosterone in sympathetic activation and increased oxidative stress associated to renovascular hypertension. Thus, this study aims to evaluate the role of aldosterone in sympathetic hyperactivity and oxidative stress in renovascular hypertensive rats (2K-1C), by chronic treatment with spironolactone (aldosterone competitive inhibitor) or losartan (AT1 receptor antagonist), in order to assess the relative contribution of each of these systems on the variables studied. For that, hemodynamic and electrophysiological recording of postganglionic sympathetic nerve activity will be analyzed in 2K-1C rats after spironolactone or losartan administration. Furthermore, to determine whether the treatments change the central oxidative stress, particularly in the major nuclei related to cardiovascular control (PVN and RVLM), the protein expression of enzymes antioxidants: superoxide dismutase, catalase, glutathione peroxidase, the AT1 receptor, mineralocorticoid receptor and the subunits of NAD(P)H oxidase: p47phox and gp91phox will be evaluated in these nuclei by Western blotting.

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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)
LINCEVICIUS, GISELE S.; SHIMOURA, CAROLINE G.; NISHI, ERIKA E.; PERRY, JULIANA C.; CASARINI, DULCE E.; GOMES, GUIOMAR N.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.. Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension. AMERICAN JOURNAL OF HYPERTENSION, v. 28, n. 9, p. 1083-1090, . (10/04333-6, 13/22522-9)

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