Inhibition of thromboxane A2-induced vasocontraction by KF4939, a new anti-platelet agent, in rabbit mesenteric and dog coronary arteries.

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Abstract
The effect of a new anti-platelet agent, KF4939, on thromboxane A2 (TXA2)-induced vasocontraction was studied in superfused rabbit mesenteric and dog coronary arteries, in comparison with the effects on the contractions evoked by KCI, noradrenaline [norepinephrine], serotonin, angiotensin II and histamine. The Ca sources involved in the TXA2-induced vasocontraction were also examined. The TXA2-induced contraction of the rabbit mesenteric artery was partly attenuated after exposure to the Ca-free medium, but was not attenuated by nifedipine. The TXA2-induced contraction of the dog coronary artery was markedly attenuated by nifedipine. TXA2 apparently utilizes both intracellularly stored Ca and an extracellular source of Ca for its vasocontraction, and the voltage-dependent Ca channel plays an important role in the dog coronary artery, but in the rabbit mesenteric artery, KF4939 inhibited the TXA2-induced contraction in both arteries. In the rabbit mesenteric artery, 3 times and more higher concentration than that to inhibit TXA2-induced one were required to inhibit other agonist induced contractions, KF4939 caused no alteration in the KCI-induced contraction of both arteries. KF4939 seems to be a selective inhibitor of TXA2-induced vasocontraction, and the receptor-linked mechanism may be a possible site of the TXA2 antagonistic action of KF4939.