Attenuated coronary relaxation after reperfusion: effects of superoxide dismutase and TxA2 inhibitor U 63557A.
Previous studies demonstrate endothelium-dependent leukotriene D4 (LTD4)-induced relaxation of canine coronary arterial rings in vitro. We now show that coronary occlusion followed by reperfusion attenuates (P less than 0.01) the relaxation of canine coronary artery rings in response to LTD4 as well as acetylcholine (ACh), suggesting loss of endothelium-dependent coronary reactivity (n = 6 dogs). Since superoxide anions have been shown to cause breakdown of endothelium-derived relaxing factor (EDRF), we wondered whether treatment of dogs with superoxide anion scavenger superoxide dismutase (SOD) would modulate the effects of LTD4 and ACh on reperfused coronary artery rings. Indeed, treatment of dogs (n = 5) with SOD before coronary reperfusion resulted in preservation of LTD4- and ACh-induced relaxation of coronary rings. Treatment of another five dogs with selective thromboxane-synthetase blocker U 63557A before coronary reperfusion also resulted in preservation of coronary ring relaxation in response to LTD4 and ACh. To determine the mechanism of U 63557A-induced preservation of coronary reactivity, canine neutrophil superoxide anion generation in the presence of U 63557A was measured. Although U 63557A had no effect on superoxide anion generation in neutrophils alone, it markedly (P less than 0.02) inhibited superoxide anion generation in neutrophils in the presence of platelets, most likely via shunting of accumulated cyclic endoperoxide in platelets toward formation of prostacyclin, which inhibits neutrophil superoxide anion production. Thus SOD and U 63557A protect against loss of endothelium-mediated vascular relaxation by LTD4 and ACh after coronary occlusion and reperfusion.
Mehta
J L
JL
Department of Medicine, University of Florida College of Medicine.
Lawson
D L
DL
Nichols
W W
WW
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001792:Blood Platelets / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015425:Myocardial Reperfusion; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013189:SRS-A / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000097:blood / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014664:Vasodilation / Q000187:drug effects*
D001572:Benzofurans; D011994:Recombinant Proteins; D013189:SRS-A; D013481:Superoxides; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; C039936:furegrelate; D000109:Acetylcholine