Effects of pre-exposure of rat vein and artery to the new no donor (RuBPY)

• Grant number: 13/07310-5
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2013
• End date: November 30, 2015
• 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
• City of the host institution: Ribeirão Preto

Abstract

Nitric oxide (NO) donors has been used in the vascular biology studies in order to understand the physiological role of NO. NO donors like nitroglycerin and sodium nitroprusside (SNP) have been used in the cardiovascular diseases. In vivo and in vitro studies demonstrated important therapeutic limitations of the nitrovasodilators. Nitroglycerin induces tolerance and SNP presents cytotoxicity due to cyanide release along NO. The tolerance to nitrates is characterized by the impaired effects on long-term administration. The cause of tolerance is not well known, but it is reported that is a multifactorial process that should involve the uncoupling of endothelial NO-synthase (NOS-3) and impaired production of NO. The nitrates such as nitroglycerin produces vasodilatation of arteries and veins but it is preferentially venodilator. Our research group has investigated the effects of several ruthenium-derived compounds. The new NO donor cis-[Ru(bpy)2(py)(NO2)](PF6), RuBPY, releases NO in vitro in the rat aorta, mesenteric resistance artery and cava vein. In contrast to SNP, this compound does not induce toxycity in the maximal concentration used to induce relaxation (EC100). In the present work, we hypothesized that the compound RuBPY does not induce tolerance in rat aorta and cava vein because it does not impair the NOS-3. The non-tolerance is also due to the vascular smooth muscle cell signaling activated by this NO donor. This study aims to investigate if RuBPY induces tolerance in vitro in aorta and cava vein and to study the cellular and molecular mechanisms involved in the RuBPY signaling on the NO-sGC-cGMP-PKG-phosphodiesterase pathway. (AU)