Cellular signaling involved in the vasodilatation induced by atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) in isolated aorta from normotensive and renal hypertensive rats

• Grant number: 09/08173-6
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2010 - July 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Lusiane Maria Bendhack
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

We have studied in our laboratory the vasodilatation induced by the activation of the soluble isoform of guanylyl-ciclase (sGC), that is activated by nitric oxide (NO). In the present work, we will study the effects of cGMP produced by the activation of particulate guanylyl-cyclase (pGC), protein kinase G (PKG) and K+ channels in the aorta from normotensive and renal hypertensive rats. Natriuretic peptides play an important role on the blood pressure homeostasis via activation of the isoforms of pGC. The ANP is mainly produced by the atrium and it is released in the blood vessels. The C- type natriuretic peptide (CNP) is present in the endothelial cells and in the vascular smooth muscle cells. ANP and CNP exert their physiological effects through the activation of the receptors NPR-A and NPR-B coupled to pGC and NPR-C or "clearance" receptor that is not linked to pGC activity. It is Gi-protein coupled receptor that activates a Ca2+-dependent nitric oxide synthase (NOS). Several studies have suggested that ANP and CNP are potential targets for the treatment of cardiovascular diseases although the data obtained in hypertensive rats are controversial. The aim of this study is to investigate the intracellular signaling involved on the vasodilatation induced by ANP and CNP in the isolated aorta from normotensive and renal hypertensive rats. Therefore, we will evaluate the vascular effects of the peptides to measure the production of cGMP via pGC and sGC, K+ channel expression, phosphorylation of the K+ channel by PKG, coimmunoprecipitation of the K+ channel and PKG, the effects of the peptides on the cytosolic [Ca2+] in the vascular smooth muscle and endothelial cells. With these studies we intend to identify the signaling pathways involved in the vasodilatation activated by NPR-A/B-pGC-cGMP-PKG- K+ channel and NO-sGC-cGMP-PKG-K+ channel in aortas from normotensive and renal hypertensive rats. (AU)