Acetylcholine induces constriction of epicardial coronary arteries in anesthetized dogs after removal of endothelium.

: The acetylcholine-induced relaxation of isolated coronary arteries is reversed to contraction in the absence of endothelium. The importance of endothelium for the regulation of coronary blood flow remains unclear. We thus tested the effects of acetylcholine on epicardial arteries and on coronary resistance vessels in situ in 8 anesthetized dogs. The left circumflex coronary artery was perfused at constant pressure. Epicardial vasomotion was evaluated by sonomicrometry, the vasomotion of coronary resistance vessels by calculated end-diastolic resistance. Acetylcholine (1 microgram/kg/min i.c.) decreased epicardial resistance by 8.6 +/- 1.6% and end-diastolic resistance by 65.8 +/- 6.3%. The epicardial coronary segment was perfused with distilled water for 65 +/- 5 s to denude it of endothelium. After removal of epicardial endothelium, the decrease in end-diastolic resistance caused by acetylcholine was unchanged (59.6 +/- 1.2%); however, epicardial resistance was increased by 7.7 +/- 1.7%. Application of glyceryl trinitrate (5 micrograms/kg/min i.c.) induced a similar decrease of epicardial resistance before and after removal of endothelium:7.9 +/- 1.4 and 6.2 +/- 1.9%, respectively. We conclude that acetylcholine-induced dilation of epicardial coronary arteries is endothelium-dependent in vivo. However, the constriction of epicardial coronary arteries in the absence of endothelium is insufficient to reduce blood flow and to induce myocardial ischemia.