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Vasodilator effect of natriuretic peptide atrial (ANP)and natriuretic peptide type-C (CNP)in isolated rat aorta.

Grant number: 09/03593-7
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2009
Effective date (End): January 31, 2011
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Lusiane Maria Bendhack
Grantee:Fernanda Aparecida de Andrade
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The natriuretic peptides play an important role in the regulation of cardiovascular homeostasis through the activation of specific isoforms of the family of enzymes, guanylate cyclase or particulate membrane. The atrial natriuretic peptide (ANP) is produced mainly by the cardiac atrium and released in the bloodstream in response to hypervolemia way of acting in endocrine regulation of blood pressure and fluid homeostasis of the body. The C-type natriuretic peptide (CNP) is found in abundance in endothelial cells of vascular smooth muscle and acts in paracrine manner to promote vasodilation and regulation of vascular tone being dependent or not the production of cGMP. Furthermore, it was recently demonstrated that CNP can act as endothelium-derived factor hiperpolarizante (EDHF) in resistance vessels of mammals thus complementing the endocrine actions of ANP, in addition to the action of other vasodilator mediators such as nitric oxide (NO) and prostacyclin . Studies on the application of ANP, CNP or drugs that act in intracellular signaling pathway of these peptides, suggest targets for therapeutic intervention to the pharmacological treatment of cardiovascular diseases such as hypertension. This project aims to investigate and evaluate the (s) possible (s) mechanism (s) cell (s) involved in the signaling pathway of CNP and ANP in the relaxation of the aorta of rats. With this aim, we various experimental protocols as functional studies of vascular reactivity to identify the possible mechanism of activation and inhibition of vasodilating, quantification and evaluation of the profile of production of cGMP by ELISA - immuno-test, measured the concentrations of cytosolic Ca2 + in vascular smooth muscle cells and endothelial cells by the technique of confocal microscopy and flow cytometry respectively, and measure the potential of cell membrane with selective fluorescent probe. These studies will identify the receptors, secondary messengers and ion channels involved in the mechanism of vascular relaxation induced by ANP and CNP on depends or independents cGMP production.