Calver A, Collier J, Vallance P
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, United Kingdom.
J Clin Invest. 1992 Dec;90(6):2548-54. doi: 10.1172/JCI116149.
Patients with insulin-dependent diabetes mellitus have an increased mortality and morbidity due to vascular complications. Nitric oxide from the vascular endothelium contributes to the control of normal vascular tone, and endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disease. In this study we have examined basal and stimulated nitric oxide-mediated vasodilatation in insulin-dependent diabetics and age- and sex-matched healthy controls. Drugs were infused locally into the brachial artery and forearm blood flow measured using venous occlusion plethysmography. Noradrenaline and NG-monomethyl-L-arginine produced similar reductions in resting forearm blood flow in healthy controls. However, in the diabetics, NG-monomethyl-L-arginine was significantly less effective than noradrenaline. Comparing between groups, the response to NG-monomethyl-L-arginine was also significantly less in the diabetics compared with the healthy controls. The response to sodium nitroprusside was significantly less in the diabetics compared with the healthy controls, whereas the responses to both acetylcholine and verapamil were the same in the two groups. The results provide evidence for an abnormality of basal nitric oxide-mediated dilatation in the forearm arterial bed of patients with insulin-dependent diabetes mellitus, and suggest that the vascular smooth muscle is less sensitive to nitric oxide.
胰岛素依赖型糖尿病患者由于血管并发症导致死亡率和发病率增加。血管内皮产生的一氧化氮有助于控制正常血管张力，并且内皮功能障碍与糖尿病血管疾病的发病机制有关。在本研究中，我们检测了胰岛素依赖型糖尿病患者以及年龄和性别匹配的健康对照者基础状态下和刺激后一氧化氮介导的血管舒张情况。将药物局部注入肱动脉，并使用静脉阻断体积描记法测量前臂血流量。在健康对照者中，去甲肾上腺素和N-单甲基-L-精氨酸使静息前臂血流量产生相似程度的降低。然而，在糖尿病患者中，N-单甲基-L-精氨酸的作用明显弱于去甲肾上腺素。在组间比较中，糖尿病患者对N-单甲基-L-精氨酸的反应也明显低于健康对照者。与健康对照者相比，糖尿病患者对硝普钠的反应明显降低，而两组对乙酰胆碱和维拉帕米的反应相同。这些结果为胰岛素依赖型糖尿病患者前臂动脉床基础一氧化氮介导的舒张异常提供了证据，并表明血管平滑肌对一氧化氮的敏感性较低。
