Effect of removing the endothelium on the vascular responses induced by leukotrienes C4 and D4 in guinea-pig isolated heart.

The coronary vascular endothelium of the guinea-pig isolated perfused heart was removed by treatment with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), a zwitterionic detergent. After CHAPS treatment of the heart the vasoconstrictor responses of leukotriene (LT) C4, LTD4 and angiotensin II (AII) were significantly attenuated whereas the vascular actions of U46619, a thromboxane (Tx) A2 mimetic, and endothelin-1 (ET-1) were unaltered. The endothelium-dependent vasoconstrictor response of LTC4 and LTD4 could not be attributed to the release of TxA2, platelet-activating factor or AII since indomethacin, WEB 2086 and captopril had no effect on LT actions. However, in the presence of cromakalim, a potassium channel activator, the vasoconstrictor effects induced by LTC4, LTD4 and AII were significantly attenuated to a greater extent than the responses of U46619 and ET-1. The results suggest that in the coronary vasculature of the guinea-pig isolated heart the vasoconstrictor responses of LTC4, LTD4 and AII are endothelium-dependent and may involve a cromakalim-sensitive mechanism.