Thromboxane A2 analogue induced coronary artery vasoconstriction in the rabbit

Diffuse coronary artery vasoconstriction was provoked in the rabbit by a stable thromboxane A2 analogue, STA2 (9,11-epithio-11,12-methano thromboxane A2). Injection of 25 micrograms.kg-1 STA2 into the left main trunk caused complete occlusion of the left anterior descending artery and narrowing of the left circumflex artery. Two minutes after injection, however, the diameter of the coronary artery returned to the control value (n = 10). The right coronary artery was also temporarily occluded by an injection of 25 micrograms.kg-1 STA2. Left ventricular end diastolic pressure increased significantly, and ST segment elevation of the electrocardiogram occurred during vasoconstriction. The angiographic findings showed that the vasoconstriction in the coronary artery induced by STA2 was similar to the diffuse vasoconstriction seen clinically. Induction of the vasoconstriction by STA2 was prevented by the preadministration of 25 micrograms.kg-1 of either a calcium antagonist, diltiazem, or a thromboxane A2 receptor antagonist, ONO 3708 (n = 10). The relation of the calcium movement to this vasoconstriction was studied in vitro using the isolated left circumflex artery in the rabbit. STA2 (50 micrograms.litre-1 to 0.5 mg.litre-1) produced a concentration dependent contraction of helical strips of left circumflex artery. Diltiazem (50-100 g.litre-1) suppressed this contraction dose dependently. ONO 3708 (10 micrograms.litre-1 to 1 mg.litre-1) caused a significant rightward and downward shift of the dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)