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.
McLeod
J D
JD
Department of Pharmacology, Hunterian Institute, Royal College of Surgeons, Lincoln's Inn Fields, London, U.K.
Piper
P J
PJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002793:Cholic Acids / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D011758:Pyrroles / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D002793:Cholic Acids; D011758:Pyrroles; D013189:SRS-A; D014665:Vasodilator Agents; D019806:Cromakalim; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate