Mechanism of prostaglandin E 2-, F 2α- and latanoprost acid-induced relaxation of submental veins

Abstract

The mechanism of prostaglandin E 2-, prostaglandin F 2α- and latanoprost acid (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F 2α)-induced relaxation of the rabbit submental vein was studied. Prostaglandin E 2 caused maximum relaxation of endothelin-1 precontracted vessels (EC 50: 1.8×10 −8 M). Much of the relaxation could be abolished by denuding the endothelium with the nitric oxide synthase inhibitor, l-NAME ( N G-Nitro- l-arginine methylester). CGRP-(8–37) (calcitonin gene-related peptide fragment (8–37)), a calcitonin gene-related peptide receptor antagonist, exhibited a partial blocking effect, whereas the tachykinin NK 1 receptor blocker, GR 82334 ([ d-Pro 9[Spiro- γ-Lactam]Leu 10,Trp 11]physalaemin (1–11)), markedly attenuated the response. Both prostaglandin F 2α and the relatively selective FP receptor agonist, latanoprost acid, caused relaxation of the veins to about 50% of the precontracted state in the presence of GR 32191B ([1 R-[1α( Z),2 β,3 β,5α]]-(+)-7-[5-([1,1′-biphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoic acid), a thromboxane receptor antagonist (EC 50: for prostaglandin F 2α 7.9×10 −9 M, and for latanoprost acid 4.9×10 −9 M). l-NAME, as well as denuding the endothelium, completely abolished the effect. In addition, most or at least a large part of the relaxation was also blocked by CGRP-(8–37) as well as GR 82334. These results indicate that the FP receptor-mediated relaxation of veins is based on release of nitric oxide in addition to involvement of calcitonin gene-related peptide and substance P, or some other tachykinin, probably released from perivascular sensory nerves. The more pronounced relaxation induced by prostaglandin E 2 could be due to vasodilator EP receptors in the smooth muscle layer of the veins.