L-arginine preferentially dilates stenotic segments of coronary arteries thereby increasing coronary flow.

Abstract

BACKGROUND AND OBJECTIVES: Oxidized LDL cholesterol and cytokines increase arginase and decrease nitric oxide (NO) synthase expression in human endothelial cells, leading to a decrease in NO production. In arteriosclerotic plaques, characterized by increased oxidized LDL and cytokine levels, a sustained local NO reduction might enhance sensitivity of the downstream guanylyl cyclase system towards an acute NO increase. We tested whether application of the NO synthase substrate l-arginine (l-arg, 150 micromol min(-1)) or the NO donor isosorbide dinitrate (ISDN; 0.3 mg) preferentially dilates stenotic coronary artery segments (CS) subsequently increasing poststenotic coronary blood flow (CBF) in patients with coronary artery disease (CAD). DESIGN, SETTING AND SUBJECTS: Changes in coronary diameter and circumferential surface area were assessed by quantitative coronary angiography (QCA) in a nonstenotic upstream segment, the CS, downstream the CS and in a reference vessel (n = 24). CBF was estimated in a subset of 13 patients by QCA and intracoronary Doppler. RESULTS: CS ranged from 62% to 89% (77 +/- 5%). l-arg increased minimal luminal diameter of the stenotic segment from 0.98 +/- 0.06 to 1.14 +/- 0.07 mm (P < 0.05) without affecting other coronary segments. Poststenotic CBF increased by 24 +/- 3%. ISDN dilated all segments again with a predominance of CS (25 +/- 4%) and increased poststenotic CBF by 38 +/- 9%. In a multifactorial anova, a medication with an angiotensin-converting enzyme inhibitor (decreasing inflammation and radical formation) and a ratio of LDL/HDL <3.5 were predictive for an l-arg-induced dilation. CONCLUSION: The increase in poststenotic CBF without affecting nondiseased arteries highlights the therapeutic potential of l-arg in patients with CAD.