EFFECT OF L-ARGININE ON HUMAN CORONARY ENDOTHELIUM-DEPENDENT AND PHYSIOLOGICAL VASODILATION

Objectives. We hypothesized that L-arginine would improve abnormal cor onary 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 c oronary vasodilation correlates with endothelial function and that L-a rginine, the substrate for nitric oxide synthesis, improves the respon se to acetylcholine (Ach). Methods. Changes in coronary blood flow and epicardial diameter response to Ach, adenosine and cardiac pacing wer e measured in 32 patients with coronary atherosclerosis or its risk fa ctors and in 7 patients without risk factors and normal coronary angio grams. Results. Intracoronary L-arginine did not alter baseline corona ry vascular tone, but the epicardial and microvascular responses to Ac h were enhanced (both p < 0.001). The improvement after L-arginine was greater in epicardial segments that initially constricted with Ach; s imilarly L-arginine abolished microvascular constriction produced by h igher doses of Ach. Thus, there mas a negative correlation between the initial epicardial and vascular resistance responses to Ach and the m agnitude of improvement with L-arginine (r = -0.55 and r = -0.50, resp ectively, p < 0.001). D-Arginine did not affect the responses to Ach, and adenosine responses were unchanged with L-arginine. Cardiac pacing -induced epicardial constriction was abolished ba L-arginine, hut micr ovascular dilation remained unaffected. Conclusions. Thus, L-arginine improved endothelium dependent coronary epicardial and microvascular f unction in patients with endothelial dysfunction. Prevention of epicar dial constriction during physiologic stress by L-arginine in patients with endothelial dysfunction may be of therapeutic value in the treatm ent of myocardial ischemia. (C) 1997 by the American College of Cardio logy.