Mechanism of prostaglandin E2-, F2alpha- and latanoprost acid-induced relaxation of submental veins.
The mechanism of prostaglandin E2-, prostaglandin F2alpha- and latanoprost acid (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha)-induced relaxation of the rabbit submental vein was studied. Prostaglandin E2 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-Pro9[Spiro-gamma-Lactam]Leu10,Trp11]physalaemin (1-11)), markedly attenuated the response. Both prostaglandin F2alpha 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-[1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy-2-(1-piperidinyl)cyclopentyl]-4-he ptenoic acid), a thromboxane receptor antagonist (EC50: for prostaglandin F2alpha 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 E2 could be due to vasodilator EP receptors in the smooth muscle layer of the veins.
Astin
M
M
Glaucoma Research Laboratories, Pharmacia and Upjohn, Uppsala, Sweden.
Stjernschantz
J
J
D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D000077338:Latanoprost; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D014680:Veins / Q000187:drug effects
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004791:Enzyme Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester