Effects of endothelium regeneration on canine coronary artery function

During coronary catheterization under general anesthesia, the endothelium of a portion of the proximal left circumflex coronary artery of dogs was removed (injured). Segments from the denuded and normal (distal circumflex and left anterior descending coronary) regions were removed immediately in some animals (acute studies) or 5 wk after the injury in other animals (chronic studies). No significant differences in passive mechanics or active stress normalized to medial thickness were found between segments from normal and denuded regions in acute studies or normal and injured segments in chronic studies. Intimal thickening was found in the chronically injured segments, which averaged 32% of the total media-adventitia thickness. No significant differences were found in potassium dose-response relations in acute or chronic studies. Maximum responses to serotonin were increased in acutely denuded but not in chronically injured segments. Sensitivity to serotonin was increased in chronically injured but not acutely denuded segments. Endothelium-dependent relaxation responses produced by acetylcholine, bradykinin, and the Ca2+ ionophore A23187 were all depressed in chronically injured segments compared with normal, as were relaxation responses to sodium nitroprusside. In acutely denuded segments, the former agents produced only small contractions at high doses, whereas nitroprusside relaxations were augmented compared with sites with intact endothelium. Relaxation responses to isoproterenol and forskolin were not significantly affected by acute denudation or by chronic injury. The results of this study suggest a "chronic" depression of relaxation responses mediated by the guanosine 3',5'-cyclic monophosphate pathway and increased serotonin vasoconstriction sensitivity in arteries 5 wk after an endothelial denudation injury.