Effect of nitric oxide donors on the contractile prostanoids in renal hypertensive rat aorta

• Grant number: 11/19499-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2011
• End date: November 30, 2013
• 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

Vascular endothelium has several physiological functions, mainly on the vascular tone control. Endothelium-derived relaxing factors (EDRFs) and endothelium-derived contractile factors (EDCFs) are produced and released from the endothelial to vascular smooth muscle cells. The major EDCFs are prostanoids such as thromboxane (TXA2), protaglandins PGE2, PGF2±. On the other hand, the most important EDRF is nitric oxide (NO), in addition to the vasodilator prostanoid PGI2 and endothelium-derived hiperpolarising factor (EDHF). In normal conditions, it occurs the equilibrium between EDCFs e EDRFs. However, in some of the cardiovascular diseases such as hypertension, it occurs endothelial dysfunction with consequent reduced NO bioavaialbility. Because NO is a radicalar specie, it rapidly reacts with other reactive oxygen species (ROS) like superoxide and peroxinitrite. The isoforms of cyclooxygenase (COX), COX-1 and COX-2 can be modulated by ROS. Recently, we have synthesized in our laboratory a new NO donor (AuNPs-{Ru-4PySH}n), that presents activity as muscarinic agonist and antioxidant. Another synthetic compound (NCX2121) has in its chemical structure a COX inhibitor (Indomethacin) and NO. Therefore, the aim of the present study is to evaluate the contribution of the endothelium for the production of ROS (superoxide and peroxinitrite) and the effect of the inhibition of COX isoforms 1 and 2, on the contractile response induced by phenylephrine (PE) or the calcium ionophore (A23187) in aorta isolated from renal hypertensive rat (2K-1C) as compared to normotensive rat aorta (2K); verify the vasodilator effect induced by the compounds NCX2121 and AuNPs-{Ru-4PySH}n in 2K and 2K-1C rat aorta pre-contracted with PE the contribution of EDCFs and ROS to the vasodilation induced by acethylcholine, NCX2121 and AuNPs-{Ru-4PySH}n. (AU)