Reperfusion after acute coronary occlusion in dogs impairs endothelium-dependent relaxation to acetylcholine and augments contractile reactivity in vitro.
Endothelial injury may contribute to the augmented coronary vascular tone seen in myocardial ischemia by impairing endothelial production or release of vasodilators. In vitro reactivity of arterial rings was studied after 60 min of coronary occlusion and 60 min of reperfusion in anesthetized dogs. Ischemia without reperfusion blunted contractile reactivity to potassium chloride (KCl), whereas ischemia plus reperfusion augmented contractile responses to both KCl and ergonovine. The response to acetylcholine, an endothelium-dependent vasodilator, was abolished in reperfused arteries, whereas the response to nitroprusside, an endothelium-independent vasodilator, was intact. Verapamil pretreatment restored KCl contractile responses to normal in reperfused coronary rings and partially restored endothelium-dependent relaxation. Electron microscopy revealed a nondenuding epicardial coronary endothelial injury in reperfused arteries. These data support the hypothesis that reperfusion of ischemic myocardium augments reactivity to vasoconstrictor agents by causing endothelial cell damage, excessive calcium influx, and loss of modulating vasodilator function.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D004727:Endothelium / Q000473:pathology / Q000503:physiopathology*; D004874:Ergonovine / Q000494:pharmacology; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D009599:Nitroprusside; D011189:Potassium Chloride; D014700:Verapamil; D000109:Acetylcholine; D004874:Ergonovine