Augmented endothelium-dependent constriction to hypoxia early and late following reperfusion of the canine coronary artery

Paul J. Pearson, Pyng J. Lin, Hartzell V Schaff, Paul M. Vanhoutte

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Abstract

1. Canine coronary arteries with intact endothelium respond to hypoxaemia or serotonin infusion with dilatation, but when the endothelium is injured 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 F(2α) 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 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 N(G)-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 N(G)-monomethyl-L-arginine. 8. These endothelium-dependent hypoxic response may play a role in the pathogenesis of hyperconstriction (vasospasm) following coronary reperfusion.

Original languageEnglish (US)
Pages (from-to)634-641
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume23
Issue number8
StatePublished - 1996
Externally publishedYes

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Keywords

  • Endothelium
  • Endothelium-derived contracting factor
  • Endothelium-derived relaxing factor
  • Hypoxia
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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