CORONARY-ARTERY RESPONSES TO PHYSIOLOGICAL STIMULI ARE IMPROVED BY DEFEROXAMINE BUT NOT BY L-ARGININE IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS WITH ANGIOGRAPHICALLY NORMAL CORONARY-ARTERIES AND NO OTHER RISK-FACTORS

Background-Acetycholine produces coronary artery (CA) constriction in diabetic patients, suggesting an impairment of endothelium-dependent d ilation. In diabetes, multiple metabolic abnormalities may inactivate nitric oxide through oxygen free radical production. Methods and Resul ts-To examine the mechanism of this abnormal response, two physiologic al tests (ie, a cold presser test [CPT] and coronary flow increase ind uced by an injection of 10 mg papaverine [PAP] in the distal left ante rior descending CA) were performed before and after either intravenous L-arginine (625 mg/minx10 minutes) or intravenous deferoxamine (50 mg /minx10 minutes) in 22 normotensive nonsmoking diabetic patients with angiographically normal CAs and normal cholesterol. Coronary surface a reas were measured with quantitative angiography. Before the administr ation of L-arginine or deferoxamine, CPT induced CA constriction ill b oth groups (-14+/-10% and -15+/-11%, respectively; each P<.001), and P AP injection in distal LAD did not modify significantly proximal LAD d imensions. In the 10 diabetic patients receiving L-arginine, responses to CPT and PAP were not modified. Conversely, in the 12 patients rece iving deferoxamine, CA dilated in response to the two tests (+10+/-9% after CPT and +22+/-7% after PAP, each P<.001). Intracoronary isosurbi de dinitrate, an endothelium-independent dilator, produced similar dil ation in tho two groups (+47+/-19% and +41+/-15%, respectively; each P <.001). Conclusions-This study shows that (1) responses of angiographi cally normal CAs to CPT and to flow increase are impaired in diabetic patients; (2) abnormal responses are not improved by L-arginine, sugge sting that a deficit in substrate fur nitric oxide synthesis is not in volved; and (3) deferoxamine restores a vasodilator response to the tw o tests, suggesting that inactivation of NO by oxygen species might be partly responsible for the impairment of CA dilation in diabetic pati ents.