VASCULAR REACTIVITY TO KININS AND EXPRESSION LEVELS OF B1 AND B2 RECEPTORS IN RATS OVEREXPRESSING THE ENDOTHELIAL B1 RECEPTOR

• Grant number: 08/05576-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2009
• End date: December 31, 2009
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Suma Imura Shimuta
• Grantee: Rafael Filippelli da Silva
• Host Institution: Departamento de Biofísica. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

It is known that kinins mediated by constitutively expressed B2 receptor, are important mediators of cardiovascular homeostasis, inflammation and nociception and the inducible B1 receptor, is responsible for the late phase and most serious states of inflammation, that may lead to several pathologies including the sepsis. Then it was of extreme importance the generation of rats overexpressing the B1 receptor specifically in the endothelium of the cells (TGR(Tie2)). The objective of this study was to pharmacologically characterize the vascular reactivity to BK and DBK, using the thoracic aorta of rats overexpressing the endothelial B1 receptors. Besides our aim is to investigate if the expression of the B2 receptors can be regulated by the high level expression of the B1 receptors. Pharmacological parameters will be determined (potency and efficacy) using the data extracted from dose-response curves for the kinins obtained from isometric relaxation recordings to evaluate the vascular reactivity to BK and DBK in the WT and TGR(Tie2)) animals. For the determination of the expression levels of the B1 and B2 receptors, the thoracic aorta will be frozen for extraction of total RNA which will be submitted to RT-PCR reaction for cDNA synthesis. From the synthesized cDNA the real time PCR reaction (qPCR) will be processed. These results might greatly help us to design new compounds to be sinthesized in order to improve the treatment of patients with inflammation and acute infections.