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

Abstract

1 TRK-100, a stable analogue of prostaglandin I₂ (PGI₂), relaxed isolated arteries of the dog precontracted with PGF_2α 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. 2 Treatment with TRK-100 attenuated the contraction induced by PGF_2α 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⁺. 3 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. 4 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.