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 —Acetylcholine produces coronary artery (CA) constriction in diabetic patients, suggesting an impairment of endothelium-dependent dilation. In diabetes, multiple metabolic abnormalities may inactivate nitric oxide through oxygen free radical production.Methods and Results —To examine the mechanism of this abnormal response, two physiological tests (ie, a cold pressor test [CPT] and coronary flow increase induced by an injection of 10 mg papaverine [PAP] in the distal left anterior descending CA) were performed before and after either intravenousl -arginine (625 mg/min×10 minutes) or intravenous deferoxamine (50 mg/min×10 minutes) in 22 normotensive nonsmoking diabetic patients with angiographically normal CAs and normal cholesterol. Coronary surface areas were measured with quantitative angiography. Before the administration ofl -arginine or deferoxamine, CPT induced CA constriction in both groups (−14±10% and −15±11%, respectively; eachP <.001), and PAP injection in distal LAD did not modify significantly proximal LAD dimensions. In the 10 diabetic patients receivingl -arginine, responses to CPT and PAP were not modified. Conversely, in the 12 patients receiving deferoxamine, CA dilated in response to the two tests (+10±9% after CPT and +22±7% after PAP, eachP <.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47±19% and +41±15%, respectively; eachP <.001).Conclusions —This study shows that (1) responses of angiographically normal CAs to CPT and to flow increase are impaired in diabetic patients; (2) abnormal responses are not improved byl -arginine, suggesting that a deficit in substrate for nitric oxide synthesis is not involved; and (3) deferoxamine restores a vasodilator response to the two tests, suggesting that inactivation of NO by oxygen species might be partly responsible for the impairment of CA dilation in diabetic patients.