| 8156634 |
Close LA, Bowman PS, Paul RJ: Reoxygenation-induced relaxation of coronary arteries. Circ Res. 1994 May;74(5):870-81.
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 oxide/endothelium-derived relaxing factor (EDRF), hydrogen peroxide, and eicosanoid pathways. In the present study, we characterize a novel endothelium-dependent component of porcine coronary artery oxygen sensitivity that is independent of these known pathways. Porcine coronary arteries were stimulated with either KCl or U46619. Hypoxia elicited a transient increase in force that was much greater in endothelium-intact arteries. This effect was abolished by nitric oxide/EDRF pathway inhibitors NG-monomethyl-L-arginine and N-nitro-L-arginine. In the steady state, hypoxia reduced isometric force to a similar degree in both intact and denuded arteries. Reoxygenation elicited a rapid and transient relaxation only in intact arteries. In contrast, this endothelium-dependent relaxation was not inhibited by nitric oxide/EDRF pathway inhibitors nor inhibitors of other potential oxygen-sensitive pathways, such as indomethacin, aminotriazole, superoxide dismutase, catalase, propranolol, or ouabain. The reoxygenation relaxation was, however, sensitive to very low levels of oxygen and was inhibited by cyanide and rotenone, suggesting an involvement of mitochondrial metabolism. Interestingly, the relaxation response to reoxygenation, similar to that for substance 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 factors may contribute to coronary artery responses to changes in oxygen partial pressure. |
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