Prostacyclin mediates arachidonic acid-induced relaxation of rabbit isolated mesenteric arteries.
Vasorelaxant effects of arachidonic acid have been attributed both to products of cyclooxygenase and alternative pathways. The present study tested whether the cyclooxygenase pathway functions to produce relaxation in mesenteric arterial rings and whether the arterial intimal layer is essential for these responses. Arachidonic acid dilated phenylephrine-contracted rings in a concentration-dependent manner. Abrasion of the intimal surface abolished the relaxant effect of arachidonic acid. The cyclooxygenase inhibitors--indomethacin, aspirin, and eicosatetraynoic acid--and a prostacyclin synthetase inhibitor, tranylcypromine, also significantly reduced or eliminated the vasodilator effect of arachidonic acid. Prostaglandins (PG) E1, E2, and I2 dilated precontracted rings whether the intimal layer was perturbed or not. Radioimmunoassayable concentrations of the stable PGI2 metabolite, 6 keto PGF1 alpha, were elevated following arachidonic acid addition in rings containing a functional endothelium. Cyclooxygenase inhibitors and tranylcypromine prevented the accumulation of 6 keto PGF1 alpha. The results are consistent with the hypotheses that arachidonic acid-induced relaxation of these rings is mediated by PGI2 and that the intimal layer is required for this conversion to PGI2.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D009637:Masoprocol; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology; D011817:Rabbits; D014191:Tranylcypromine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism*
D001095:Arachidonic Acids; D002396:Catechols; D016861:Cyclooxygenase Inhibitors; D008688:Methacholine Compounds; D011453:Prostaglandins; D014665:Vasodilator Agents; D016210:Methacholine Chloride; D016718:Arachidonic Acid; D009569:Nitric Oxide; D014191:Tranylcypromine; D009637:Masoprocol; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases