|Support type:||Scholarships in Brazil - Doctorate|
|Effective date (Start):||June 01, 2012|
|Effective date (End):||May 31, 2016|
|Field of knowledge:||Biological Sciences - Physiology - General Physiology|
|Principal Investigator:||Margarida de Mello Aires|
|Grantee:||Regiane Cardoso Castelo Branco|
|Home Institution:||Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil|
The actions of Ang-(1-7) in the kidney are not well understood: some admit they may be via receptor MAS and others via Mas plus AT1 and/or AT2. In our recent Master (see attached work), we demonstrated that in the proximal tubule Ang-(1-7), via MAS, has a biphasic effect: low dose inhibits the Na+/H+ exchanger (NHE3 isoform) increasing a lot the [Ca2+]i and high doses stimulates the exchanger increasing little the [Ca2+]i. Considering - i.) the role of NHE3 in the regulation of ECV, ii.) the influence of [Ca2+]i in the exchanger, iii.) the biphasic effect we found for Ang-(1-7) is the opposite of that described for Ang II and iv.) plasma concentrations of these hormones vary with the changes of ECV - we will study the acute effects of intratubular microperfusion of both hormones (10-9 or 10-6 M) and/or antagonists of MAS, AT1 and AT2 on NHE3 and [Ca2+]i in the in vivo proximal tubule of Wistar rats (normotensive). Since - i.) the important role of the RAS in the pathophysiology of cardiovascular and renal disease, and ii.) in these diseases, the beneficial effects of Ang-(1-7) are opposite to the deleterious effects of Ang II - we will use also hypertensive rats (SHR ) and their control Wistar-Kyoto (WKY). To contribute to the understanding of the etiology of hypertension, we will investigate the effects of 28 days of continuous infusion of 400 ng.kg.min of Ang-(1-7) and/or 41.66 ng.kg.min of A779 (an inhibitor of MAS) on renal function in Wistar, SHR and WKY rats by clearances and by quantifying the expression of ACE, ACE2, Mas, AT1 and AT2 by Western blotting of kidney tissue. As the increase of AP of these rats depends on age, they will be studied between 12-16 or 20-24 weeks.