PRESERVED VASODILATOR RESPONSE TO ACETYLCHOLINE IN ATHEROSCLEROTIC CORONARY-ARTERIES BEFORE AND AFTER PTCA

The vascular response to local administration of acetylcholine is used , clinically, to assess endothelial function in vivo. However, whether this response predominantly reflects the functional state of the vasc ular endothelium, or rather results from smooth muscle reactivity per se is not clear. In 15 patients with chronic stable angina and angiogr aphically significant coronary disease, we studied the effects of incr easing doses of intracoronary acetylcholine (5, 10, 30, 50, and 80 mu g) and nitroglycerin (200 mu g) on coronary vasular tone. In three pat ients the protocol was performed at the time of diagnostic coronary an giography and 7 and 24 hours after angioplasty. The remaining five und erwent acetylcholine administration before and after percutaneous tran sluminal coronary angioplasty (PTCA). We quantitatively assessed the d iameter of 54 coronary arterial segments; 12 stenotic segments, 13 pos t-PTCA segments with residual irregularities, 18 reference segments of the same arteries taken proximal to the stenosis or to the dilatation site, and 11 remote segments of nonstenotic vessels. They all showed a bimodal response to acetylcholine. At the lowest concentration (5 mu ) the agent invariably caused dilatation (9.22 +/- 6.55%), which was n ot significantly different in the various segments and was always less than that induced by nitroglycerin (24.56 +/- 12.82%, P < 0.0001). At the highest doses (50 or 80 mu g) acetylcholine always induced vasoco nstriction, which was significantly more pronounced in the post-PTCA ( -31.54 +/- 10.65%) and stenotic segments (-23.08 +/- 11.88%) than in t he reference and remote segments (respectively, -14.88 + 7.63% and -18 .67 + 8.37%, P < 0.05). We conclude that: (1) some degree of endotheli al dependent vasodilatation is preserved even in the presence of ather oma and intimal injury induced by angioplasty; (2) atheroma and especi ally acute intimal injury augment the vasoconstrictor response to high dose acetylcholine, the effect being most probably mediated by primar y smooth muscle supersensitivity; (3) since acetylcholine has direct a nd endothelium-mediated vasoactive effects, this agent may not be the ideal one for testing endothelial integrity.