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 hypoxaemia or serotonin infusion with dilatation, but when the endothelium is injured or dysfunctional, these stimuli can cause constriction. The present studies investigated whether or not regional ischaemia and reperfusion alter endothelium-dependent responsiveness of canine coronary arteries in vivo and in vitro. 2. In organ chamber experiments, isolated control and reperfused coronary artery rings were contracted with prostaglandin F2 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 NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis from L-arginine. 4. These findings demonstrate that early following coronary reperfusion the hypoxic augmentation, which is mediated by a nitric oxide-dependent pathway in the endothelium, is facilitated. 5. In vivo studies revealed hyperconstriction of reperfused arteries in response to hypoxaemia (PO2 = 30-40 mmHg) and administration of either serotonin or ergonovine. 6. Twelve weeks following reperfusion injury, coronary arteries still exhibited augmented endothelium-dependent hypoxic augmentations in vitro, which were inhibited by NG-monomethyl-L-arginine. 7. Furthermore, resting coronary segments with endothelium displayed hypoxia-induced contractions that could not be inhibited by indomethacin, the lipoxygenase inhibitor AA861, superoxide dismutase plus catalase, deferoxamine, ouabain, or NG-monomethyl-L-arginine. 8. These endothelium-dependent hypoxic response may play a role in the pathogenesis of hyperconstriction (vasospasm) following coronary reperfusion.
Pearson
P J
PJ
Section of Cardiovascular Surgery and Cardiac Surgical Research, Mayo Clinic, Rochester, Minnesota, USA.
Lin
P J
PJ
Schaff
H V
HV
Vanhoutte
P M
PM
D000704:Analysis of Variance; D000818:Animals; D015687:Cell Hypoxia; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007511:Ischemia; D015425:Myocardial Reperfusion; D009569:Nitric Oxide / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide