Effect of image-Arginine on Human Coronary Endothelium-Dependent and Physiologic Vasodilation

Objectives. We hypothesized that image-arginine would improve abnormal coronary vasodilation in response to physiologic stress in patients with atherosclerosis and its risk factors by reversing coronary endothelial dysfunction. Background. Studies have demonstrated that physiologic coronary vasodilation correlates with endothelial function and that image-arginine, the substrate for nitric oxide synthesis, improves the response to acetylcholine (Ach). Methods. Changes in coronary blood flow and epicardial diameter response to Ach, adenosine and cardiac pacing were measured in 32 patients with coronary atherosclerosis or its risk factors and in 7 patients without risk factors and normal coronary angiograms. Results. Intracoronary image-arginine did not alter baseline coronary vascular tone, but the epicardial and microvascular responses to Ach were enhanced (both p < 0.001). The improvement after image-arginine was greater in epicardial segments that initially constricted with Ach; similarly, image-arginine abolished microvascular constriction produced by higher doses of Ach. Thus, there was negative correlation between the initial epicardial and vascular resistance responses to Ach and the magnitude of improvement with image-arginine (r = −0.55 and r = −0.50, respectively, p < 0.001). image-Arginine did not affect the responses to Ach, and adenosine responses were unchanged with image-arginine. Cardiac pacing-induced epicardial constriction was abolished by image-arginine, but microvascular dilation remained unaffected. Conclusions. Thus, image-arginine improved endothelium-dependent coronary epicardial and microvascular function in patients with endothelial dysfunction. Prevention of epicardial constriction during physiologic stress by image-arginine in patients with endothelial dysfunction may be of therapeutic value in the treatment of myocardial ischemia.