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 vascular endothelium, or rather results from smooth muscle reactivity per se is not clear. In 15 patients with chronic stable angina and angiographically significant coronary disease, we studied the effects of increasing doses of intracoronary acetylcholine (5, 10, 30, 50, and 80 mu g) and nitroglycerin (200 mu g) on coronary vasular tone. In three patients the protocol was performed at the time of diagnostic coronary angiography and 7 and 24 hours after angioplasty. The remaining five underwent acetylcholine administration before and after percutaneous transluminal coronary angioplasty (PTCA). We quantitatively assessed the diameter of 54 coronary arterial segments; 12 stenotic segments, 13 post-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 not 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 vasoconstriction, which was significantly more pronounced in the post-PTCA (-31.54 +/- 10.65%) and stenotic segments (-23.08 +/- 11.88%) than in the reference and remote segments (respectively, -14.88 + 7.63% and -18.67 + 8.37%, P < 0.05). We conclude that: (1) some degree of endothelial dependent vasodilatation is preserved even in the presence of atheroma and intimal injury induced by angioplasty; (2) atheroma and especially acute intimal injury augment the vasoconstrictor response to high dose acetylcholine, the effect being most probably mediated by primary smooth muscle supersensitivity; (3) since acetylcholine has direct and endothelium-mediated vasoactive effects, this agent may not be the ideal one for testing endothelial integrity.