Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries

Abstract

Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 × 10 −7, 10 −6 and 5 × 10 −6 M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10 −3 M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching −48.5 ± 17% at 5 × 10 −6 M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to −21 ± 9% at 5 × 10 −6 M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 ± 12% at 5 × 10 −7 M (p < 0.01) and decreasing by 21 ± 13% at 5 × 10 −6 M (p < 0.05). Infusion of L-arginine was associated with a 15 ± 11% increase in coronary blood flow (p < 0.01). The simultaneous infusion of acetylcholine resulted in an increase in coronary blood flow of 53 ± 12% (p < 0.01) and of 17 ± 11% (p < 0.05) at 5 × 10 −7 M and 5 × 10 −6 M, respectively. Consequently, in response to 5 × 10 −6 M acetylcholine, coronary resistance increased by 53 ± 17% during control conditions (p < 0.01) whereas it tended to decrease (−8.5 ± 15%) during simultaneous infusion of L-arginine. The results show that, in patients with coronary artery disease, intracoronary infusion of L-arginine alleviates the vasoconstrictor action of acetylcholine, suggesting improvement of endothelium-dependent relaxation in coronary arteries.