Involvement of thromboxane and leukotriene in arachidonate induced coronary constriction in diabetic rats

Vascular responsiveness to sodium arachidonate was examined in isolated perfused hearts from rats with streptozotocin-induced diabetes. In diabetic rats arachidonate induced a biphasic coronary vascular response characterized by initial vasoconstriction followed by prolonged vasodilation. Non-diabetic rats showed only a vasodilator response. The vasoconstrictor phase found in diabetic rats was abolished by ONO-3708, a selective thromboxane A2 antagonist. Indomethacin partly inhibited the vasoconstrictor response, the residual response being abolished by a leukotriene antagonist, ONO-1078. The vasodilator response, however, was completely abolished by indomethacin in both diabetic and nondiabetic rats. Furthermore, the coronary constrictor response to leukotriene D4 was enhanced in diabetic compared to nondiabetic rats. These results suggest an involvement of leukotriene in the vasoconstrictor response to arachidonate in diabetic rats, especially when cyclooxygenase is inhibited.