Direct vasoconstriction and endothelium-dependent vasodilation. Mechanisms of acetylcholine effects on coronary flow and arterial diameter in patients with nonstenotic coronary arteries.

Abstract

An endothelium-dependent vasodilator response to acetylcholine has been described recently in patients with coronary artery disease. Those studies determined responses only of large epicardial arteries. Our study was designed to determine the integrated effects of acetylcholine on epicardial diameter, coronary flow, and vascular resistance. Patients (n = 64) with nonstenotic epicardial coronaries underwent coronary angiography with simultaneous recording of coronary flow velocity using a 3F subselective Doppler catheter. Measurements of epicardial arterial cross-sectional area (ECA), velocity, estimated flow (velocity times area), and vascular resistance were made before and after bolus administration of acetylcholine (100 micrograms i.c.). Similar measurements were made after papaverine (12-15 mg i.c.), a nonendothelium-dependent vasodilator. Acetylcholine resulted in a reduction of ECA of 19 +/- 3%, whereas papaverine increased ECA by 9 +/- 2%. Estimated flow increased 69 +/- 12% after acetylcholine and 147 +/- 12% after papaverine. Resistance fell after both agents (acetylcholine, -17 +/- 13%; papaverine, -61 +/- 2%). Transvascular resistance fell after acetylcholine in all but five patients. These patients had dramatic epicardial artery constriction (40 +/- 8% decrease in ECA). The effect of acetylcholine on both ECA and resistance was blocked by atropine (1 mg i.c.). Nitroglycerin (300 micrograms i.c.) resulted in epicardial dilatation (7.5 +/- 2.8%) in the same patients in whom acetylcholine caused constriction (-11.2 +/- 3.1%).(ABSTRACT TRUNCATED AT 250 WORDS)