Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis

Abstract

To determine if L-arginine, a precursor of the endothelium-derived relaxing factor, restores endothelium-dependent dilation in human coronary arteries, we studied 21 patients in whom the lumina of the coronary arteries were angiographically smooth or slightly irregular and in whom there was a constrictor response to acetylcholine (ACh) in the left anterior descending coronary artery or the circumflex coronary artery. We examined the response to intracoronary ACh before and after infusion of L-arginine by measuring coronary diameter with quantitative angiography. Intracoronar injection of ACh produced vasoconstriction in the majority of patients with coronary risk factors. The percentage diameter change in smooth segments in patients with entirely smooth coronary arteries (group 1, n = 44) from baseline was −20.7% ± 17.4%. During systemic infusion of L-arginine, the constrictor response to ACh in these segments was significantly attenuated (−2.2% ± 15.1% from baseline, p < 0.01, ACh alone vs ACh during L-arginine infusion). In smooth segments in patients with luminal irregularities in the other coronary arteries (group 2, n = 19), ACh produced a marked constriction (−32.5% ± 22.5% from baseline, p < 0.05, group 1 vs group 2). Infusion of L-arginine also attenuated ACh-induced vasoconstriction in these segments (−9.7% ± 14.1% from baseline, p < 0.01, ACh vs ACh during L-arginine infusion). In segments with irregular lumina (group 3, n = 26), ACh produced more prominent vasoconstriction. The percentage diameter change was −40.9% ± 26.5% from baseline ( p < 0.01 vs group 1). In contrast, infusion of L-arginine did not attenuate ACh-induced vasoconstriction in these segments (−41.2% ± 26.9% from baseline). Infusion of L-arginine alone did not affect coronary diameter either in smooth or in irregular segments. L-arginine did not augment the dilator response to ACh in normal segments ( n = 7) (15.4% ± 9.7% vs 16.3% ± 10.6%, p not significant [NSJ ACh vs ACh during L-arginine infusion). The endothelium-independent vasodilation by isosorbide dinitrate was well preserved in all coronary segments examined (30.4% ± 21.2% in group I, 26.1% ± 18.1% in group 2, and 32.6% ± 20.6% in group 3; p NS). We conclude that exogenous L-arginine reverses ACh-induced vasoconstriction in human coronary arteries in the early stages of atherosclerosis, whereas L-arginine does not reverse the response in the advanced stage of atherosclerosis.