Vasodilator actions of TRK‐100, a new prostaglandin I2 analogue

Abstract

TRK‐100, a stable analogue of prostaglandin I2 (PGI2), relaxed isolated arteries of the dog precontracted with PGF2α or K+; the relaxation was in the order of mesenteric and renal > coronary and femoral > basilar and middle cerebral arteries. The relaxation by TRK‐100 was not affected by treatment with atropine, propranolol, cimetidine, aminophylline, and indomethacin, but was suppressed by diphloretin phosphate, a prostaglandin antagonist. Treatment with TRK‐100 attenuated the contraction induced by PGF2α and Ca2+ in mesenteric and basilar arteries previously exposed to Ca2+‐free medium, but did not significantly alter the contractile response to Ca2+ in the arteries exposed to Ca2+‐free medium and depolarized by excess K+. TRK‐100 and nitroglycerin relaxed isolated mesenteric arteries to a similar extent; however, when continuously infused into mesenteric arteries in anaesthetized dogs, TRK‐100 produced greater vasodilatation than nitroglycerin. It is concluded that TRK‐100 relaxes dog mesenteric and renal arteries more than cerebral arteries; the relaxation appears to derive from interference with the release of Ca2+ from intracellular stores and with the transmembrane Ca2+ influx through a receptor‐operated channel. TRK‐100 may vasodilate large and small mesenteric arteries and resistance vessels to a similar extent, whereas nitroglycerin preferentially dilates the large artery. 1986 British Pharmacological Society