Nitenberg A, Paycha F, Ledoux S, Sachs R, Attali J R, Valensi P
Service de Physiologie et d'Explorations Fonctionnelles, INSERM, Hôpital Louis Mourier, CHU Xavier-Bichat, Colombes, France.
Circulation. 1998 Mar 3;97(8):736-43. doi: 10.1161/01.cir.97.8.736.
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.
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).
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.
乙酰胆碱可使糖尿病患者的冠状动脉（CA）收缩，提示内皮依赖性舒张功能受损。在糖尿病中，多种代谢异常可能通过产生氧自由基使一氧化氮失活。
为研究这种异常反应的机制，对22例血压正常、不吸烟、冠状动脉造影正常且胆固醇正常的糖尿病患者，在静脉注射L-精氨酸（625mg/min×10分钟）或静脉注射去铁胺（50mg/min×10分钟）前后，进行了两项生理学试验（即冷加压试验[CPT]和在左前降支远端冠状动脉注射10mg罂粟碱[PAP]诱导的冠状动脉血流增加）。用定量血管造影测量冠状动脉表面积。在给予L-精氨酸或去铁胺之前，CPT在两组中均诱导冠状动脉收缩（分别为-14±10%和-15±11%；P均<0.001），在左前降支远端注射PAP对近端左前降支直径无显著影响。在10例接受L-精氨酸的糖尿病患者中，对CPT和PAP的反应未改变。相反，在12例接受去铁胺的患者中，冠状动脉在两项试验后均扩张（CPT后为+10±9%，PAP后为+22±7%；P均<0.001）。冠状动脉内注射硝酸异山梨酯，一种不依赖内皮的扩张剂，在两组中产生相似的扩张（分别为+47±19%和+41±15%；P均<0.001）。
本研究表明：（1）冠状动脉造影正常的糖尿病患者的冠状动脉对CPT和血流增加的反应受损；（2）L-精氨酸不能改善异常反应，提示一氧化氮合成底物缺乏不参与其中；（3）去铁胺恢复了对两项试验的血管舒张反应，提示氧自由基使一氧化氮失活可能部分导致糖尿病患者冠状动脉扩张受损。
