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.


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 intravenous L-arginine (625 mg/min x 10 minutes) or intravenous deferoxamine (50 mg/min x 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 of L-arginine or deferoxamine, CPT induced CA constriction in both groups (-14 +/- 10% and -15 +/- 11%, respectively; each P<.001), and PAP injection in distal LAD did not modify significantly proximal LAD dimensions. In the 10 diabetic patients receiving L-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, each P<.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47 +/- 19% and +41 +/- 15%, respectively; each P<.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 by L-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.
Nitenberg
A
A
Service de Physiologie et d'Explorations Fonctionnelles, INSERM, Hôpital Louis Mourier, CHU Xavier-Bichat, Colombes, France.
Paycha
F
F
Ledoux
S
S
Sachs
R
R
Attali
J R
JR
Valensi
P
P
D000328:Adult; D000931:Antidotes / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D003080:Cold Temperature; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010208:Papaverine / Q000008:administration & dosage; D012307:Risk Factors; D013312:Stress, Physiological / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000008:administration & dosage; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology
D000931:Antidotes; D007502:Iron Chelating Agents; D014665:Vasodilator Agents; D001120:Arginine; D010208:Papaverine; D003676:Deferoxamine