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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 &lt;.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 &lt;.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47±19% and +41±15%, respectively; eachP &lt;.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.

circulation

Coronary Artery Responses to Physiological Stimuli Are Improved by Deferoxamine but not by <scp>l</scp> -Arginine in Non–Insulin-Dependent Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Risk Factors

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