Vascular relaxation endothelium-dependent by the prostacyclin receptors activation

• Grant number: 18/09588-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2018
• End date: August 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Tayná Frigel Kikugava
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Prostacyclin (PGI2) is produced in vascular endothelial cells and acts by IP prostacyclin receptor activation to cause vasodilation and inhibit smooth muscle cell proliferation and platelet aggregation. In addition to nitric oxide (NO), prostanoids play an important role on the vascular tone control. Prostanoids are produced by COX isoforms that metabolize arachidonic acid to PGG2 and PGH2. PGH2 is the common substrate for various prostaglandin- synthases to form PGI2 and thromboxane A2, among other products. PGI2 activates IP receptors IP leading to vasodilatation and TXA2 activates TP receptors inducing vasoconstriction. The enzymes COX and eNOS are expressed in the endothelial cells and the activation of both enzymes are calcium-dependent. The hypothesis of this work is that the PGI2 recptors agonist (Iloprost) activates IP receptor inducing rat aorta relaxation in an endothelium-dependent way. It occurs calcium-dependent modulation between the enzymes COX and eNOS. This study aims to evaluate the vascular relaxation induced by the IP receptors activation with iloprost in rat aorta. Therefore, we will perform concentration-effect curves for the agonist iloprost in rat aorta rings with or without endothelium, in the absence or in the presence of the COX inhibitor (ibuprofen) and in the absence or in the presence of eNOS inhibitor (L-NAME). The pharmacological parameters of eficacy (Emax) and potency (pD2) of the agonist iloprost in inducing relaxation of the pre-contraction stimulated with phenylephrine.