Effect of sodium nitroprusside and Terpy in NO release and generation of reactive oxygen species in endothelial and vascular smooth muscle cells

• Grant number: 13/17124-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2013
• End date: November 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Michele Paulo Schiavi
• Grantee: Luiz Antonio Zanin Junior
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The nitric oxide (NO) donor compounds are widely used as antihypertensive drugs. They enable an increase in NO concentration, which has a relaxing action on smooth muscle and promotes vasodilation as well. However, some of these NO donors may interfere with the physiological processes by modifying the endogenous production of NO. It has been shown that [Ru (terpy) (bdq) NO] 3 + (terpy), causes the uncoupling of eNOS, leading to reactive oxygen species (O2-) formation, which has a vasoconstrictor effect. The reactive oxygen species, and its potential vasoconstrictor effect, also interfere with the NO generation and its biodisponibility. For example, O2- can react directly with NO or promote eNOS uncoupling. Previous studies conducted by our research group demonstrated that the presence of endothelium reduced the vasodilator effect of therapy. In contrast, it was observed that sodium nitroprusside (SNP) had its vasodilating effect potentiated in the presence of endothelium. The hypothesis of this study is that therapy promotes an increase of reactive oxygen species (especially O2-) generation in endothelial cells. However, the SNP is not expected to increase O2- in endothelial and vascular smooth muscle cells. About NO release, it is expected that both NO donors will increase NO concentration in both endothelial and vascular smooth muscle cells. The objective of this work is to study the generation of reactive oxygen species in muscle and endothelial cells stimulated with SNP and therapy. In addition, we will also evaluate the release of NO in these cells after stimulation with NO donors. (AU)