Clinical investigation
Contribution of endothelium-derived nitric oxide to coronary arterial distensibility: An in vivo two-dimensional intravascular ultrasound study

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Abstract

Reduced epicardial coronary arterial disteinsibility associated with early atherosclerosis may be mediated in part by reduced nitric oxide (NO) release. To directly assess the contribution of endogenous NO to coronary arterial distensibility, we examined the effect of intracoronary Nω nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, and l-arginine, its natural substrate, on the circumflex artery in seven anesthetized dogs. We also used intracoronary acetylcholine to examine the effect of pharmacologically induced NO release on coronary distensibility. Electrocardiographically gated measurements of epicardial coronary lumen area were made by a blinded observer from images obtained with a 4.3F, 30 MHz intravascular ultrasound catheter. Aortic root pressure was continuously monitored, and neither systemic arterial pressure nor pulse pressure changed significantly with intracoronary drug administration. Change in lumen area (ΔLA) from end systole to end disatole was measured, and an arterial distensibility index was calculated. ΔLA increased with acetylcholine from 8.2% ± 0.5% at baseline to 16.3% ± 2.8% (10−6 mol/L; p < 0.001), with increases in both end-systolic and end-diastolic lumen area. l-NAME (10−4 mol/L) decreased both end-systolic and end-diastolic lumen area and decreased ΔLA to 3.1% ± 1.3% (p < 0.01) Lumen area and ΔLA were both restored to baseline by l-arginine (10−4). The calculation distensibility index of the epicardial coronary artery was enhanced by acetylcholine, reduced below baseline by l-NAME, and restored to baseline by l-arginine. Balloon denudation of the left anterior descending coronary artery caused small increases in end-systolic and end-diastolic lumen areas, but decreased ΔLA in the denuded segment (to 4.4% ± 1.4%, p < 0.01) and the coronary artery distensibility index. Thus epicardial coronary artery distensibility is modulated by both basal and induced release of endothelium-derived NO. The endothelial dysfunction associated with early atherosclerosis may thus decrease coronary arterial distensibility even before structural changes in the blood vessels.

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    Dr. Sudhir was funded as a C. J. Martin Fellow by the National Health & Medical Research Council of Australia and as a Postdoctoral Fellow by the American Heart Association, California Affiliate.

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