Increased vasoconstrictor activity of proximal coronary arteries with endothelial damage in intact dogs

In this study we examined the hypothesis that endothelial damage increases proximal coronary arterial vasomotor tone and sensitivity to vasoconstrictor stimulation. The response of the left anterior descending coronary artery (LAD) (% area change) to serotonin and nitroglycerin were examined in eight anesthetized (Innovar + nitrous oxide), closed-chest dogs by means of quantitative coronary angiography. Dose-response curves of percent change in arterial cross-sectional area for three doses of intracoronary serotonin were examined before and after endothelial damage produced by a balloon catheter in the LAD. Endothelial damage was verified by postmortem scanning electron microscopic examination. Intracoronary injection of 133Xe provided coronary flow data. The damaged segment of LAD showed spontaneous vasoconstriction and further constriction in response to serotonin (33 +/- 5% before and 52 +/- 6% area reduction after damage; p less than .05). Nitroglycerin reversed serotonin-induced vasoconstriction in LAD segments without damage but not in the LAD segment with endothelial damage. No significant changes were observed in aortic pressure, and heart rate was kept constant by pacing. Blood flow in the LAD was not affected by endothelial damage itself (control, 2.44 +/- 0.09 ml/min/g; damage, 2.53 +/- 0.22 ml/min/g). Endothelial damage induced spontaneous proximal coronary constriction and diminished the relaxant response to nitroglycerin in the presence of serotonin. These results suggest that focal coronary narrowing that occurs in some patients after provocation with vasoconstrictor agents may be caused by local areas of damaged endothelium.