REOXYGENATION-INDUCED RELAXATION OF CORONARY-ARTERIES - A NOVEL ENDOTHELIUM-DEPENDENT MECHANISM

Coronary artery contractility is well known to be modulated by oxygen partial pressure. Both smooth muscle and the endothelium contribute to coronary artery oxygen sensitivity. Mechanisms underlying endothelium -dependent effects of oxygen include the sensitivity of the nitric oxi de/endothelium-derived relaxing factor (EDRF), hydrogen peroxide, and eicosanoid pathways. In the present study, we characterize a novel end othelium-dependent component of porcine coronary artery oxygen sensiti vity that is independent of these known pathways. Porcine coronary art eries were stimulated with either KCl or U46619. Hypoxia elicited a tr ansient increase in force that was much greater in endothelium-intact arteries. This effect was abolished by nitric oxide/ EDRF pathway inhi bitors N-G-monomethyl-L-arginine and N-nitro-L-arginine. In the steady state, hypoxia reduced isometric force to a similar degree in both in tact and denuded arteries. Reoxygenation elicited a rapid and transien t relaxation only in intact arteries. In contrast, this endothelium-de pendent relaxation was not inhibited by nitric oxide/EDRF pathway inhi bitors nor inhibitors of other potential oxygen-sensitive pathways, su ch as indomethacin, aminotriazole, superoxide dismutase, catalase, pro pranolol, or ouabain. The reoxygenation relaxation was, however, sensi tive to very low levels of oxygen and was inhibited by cyanide and rot enone, suggesting an involvement of mitochondrial metabolism. Interest ingly, the relaxation response to reoxygenation, similar to that for s ubstance P, could be restored in denuded arteries by coupling with an endothelium-intact donor artery. This ''sandwich'' experiment suggests that the endothelium dependence is mediated by a transmissible factor . Our results indicate that a novel class of endothelium-dependent fac tors may contribute to coronary artery responses to changes in oxygen partial pressure.