Mechanism of prostaglandin E2-, F2α- and latanoprost acid-induced relaxation of submental veins

The mechanism of prostaglandin E-2-, prostaglandin F-2 alpha- and latanoprost acid (13,14-dihydro-1 7-phenyl-18,19,20-trinor-prostaglandin F-2 alpha)-induced relaxation of the rabbit submental vein was studied. Prostaglandin E-2 caused maximum relaxation of endothelin-1 precontracted vessels (EC50: 1.8 X 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 NK1 receptor blocker, GR 82334 ([D-Pro(9)[Spiro-gamma-Lactam]Leu(10),Trp(11)]physalaemin (1-11)), markedly attenuated the response. Both prostaglandin F-2 alpha 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 ([1R-[1 alpha(Z),2 beta,3 beta,5 alpha]]-(+)-7-[5-([1,1'-biphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-heptenoic acid), a thromboxane receptor antagonist (EC50: for prostaglandin F-2 alpha 7.9 X 10(-9) M, and for latanoprost acid 4.9 x 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. (C) 1997 Elsevier Science B.V.