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Cellular mechanims activated by endogenous agonists in the aorta of renal hypertensive rats with endothelial dysfunction

Grant number: 12/16392-2
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): November 01, 2012
Effective date (End): July 31, 2014
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Lusiane Maria Bendhack
Grantee:Ana Carolina Campos Cotrim Bocalon
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The sympathetic nervous system (SNS) plays a crucial role on the arterial pressure control by activation of efferent fibers and adrenal medulla. In the order hand Vascular endothelium has important role on the vascular tone control by EDRFs and EDCFs release. Renal hypertension (2K-1C) is related to increased production of reactive oxygen species (ROS), SNS hyperactivity and endothelial dysfunction. The sympathetic hyperactivity leads to catecholamines release in the vessels that could be related to the vascular modulation. In previous studies our group has shown lower contraction induced by phenylephrine in 2K-1C than in 2K rat aorta dependent effect of eNOS activity. In the present work, our hypothesis is that the endothelium modulates the response induced by the endogenous adrenergic agonists that involves the activation of others adrenoceptors than ±1-adrenoceptors. This study aims to evaluate the role of the endothelial factors and ROS on the vascular reactivity responses induced by the endogenous agonists noradrenaline (NOR) and adrenaline (ADR) in 2K and 2K-1C rats aorta. We will measure the plasma concentrations of NOR and ADR. Concentration- effect curves will be constructed for NOR and ADR in denuded and intact endothelium aorta from 2K and 2K-1C. Selective and non-selective antagonists, in combination or alone, will be used in order to identify the adrenoceptors involved in the endothelial modulation. The inhibition of NO-Sinthase and COX will be studied by using L-NAME and ibuprofen. The production of ROS and NO Will be measured by flow cytometry in isolated endothelial cells from 2K and 2K-1C aorta, stimulated with NOR or ADR in the presence or absence of the antagonists and vitamin C, and by imuno-histochemistry we will investigate the adrenoceptors localization in both endothelial and vascular smooth muscle cells. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BOCALON, Ana Carolina Campos Cotrim. Cellular mechanisms activated by adrenergic agonists in the aorta of renal hypertensive rats with endothelial dysfunction. 2014. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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