AUGMENTED ENDOTHELIUM-DEPENDENT CONSTRICTION TO HYPOXIA EARLY AND LATE FOLLOWING REPERFUSION OF THE CANINE CORONARY-ARTERY

1. Canine coronary arteries with intact endothelium respond to hypoxae mia or serotonin infusion with dilatation, but when the endothelium is injured or dysfunctional, these stimuli can cause constriction. The p resent studies investigated whether or not regional ischaemia and repe rfusion alter endothelium-dependent responsiveness of canine coronary arteries in vivo and in vitro. 2. In organ chamber experiments,isolate d control and reperfused coronary artery rings were contracted with pr ostaglandin F-2 alpha and exposed to hypoxia (PO2 less than 5 mmHg). 3 . Hypoxia augmented the response of reperfused arteries more than that of controls. The hypoxic augmentation was blocked by N-G-monomethyl-L -arginine, an inhibitor of nitric oxide synthesis from L-arginine. 4. These findings demonstrate that early following coronary reperfusion t he hypoxic augmentation, which is mediated by a nitric oxide-dependent pathway in the endothelium, is facilitated. 5. In vivo studies reveal ed hyperconstriction of reperfused arteries in response to hypoxaemia (PO2 = 30-40 mmHg) and administration of either serotonin or ergonovin e. 6. Twelve weeks following reperfusion injury, coronary arteries sti ll exhibited augmented end of helium-dependent hypoxic augmentations i n vitro, which were inhibited by N-G-monamethyl-L-arginine. 7. Further more, resting coronary segments with endothelium displayed hypoxia-ind uced contractions that could not be inhibited by indomethacin, the lip oxygenase inhibitor AA861, superoxide dismutase plus catalase, deferox amine, ouabain, or N-G-monomethyl-L-arginine. 8. These endothelium-dep endent hypoxic response may play a role in the pathogenesis of hyperco nstriction (vasospasm) following coronary reperfusion.