NITRIC OXIDE IN ENDOTHELIUM-DEPENDENT VASODILATION IN HYPERCHOLESTEROLEMIA

最近的研究表明，内皮依赖性血管 高胆固醇血症动物和人的松弛受损。 我们 进行了目前的调查，以确定一氧化氮的作用， 内皮细胞产生的几种因子之一，在这种异常的 血管舒张剂对内皮依赖性药物的反应。 为此目的， 我们研究了抑制剂NG-单甲基-L-精氨酸（L-NMMA） 内皮细胞合成一氧化氮的能力， 张力和对乙酰胆碱的反应（内皮依赖性 血管扩张剂）和硝普钠（平滑肌扩张剂）。 二十 高胆固醇血症患者（血浆胆固醇> 240 mg/dl;年龄49 ± 8 18例正常对照组（47 ± 7岁，男性11例，女性7例）， 7名妇女）。 将药物注入肱动脉， 通过应变仪体积描记法测量前臂脉管系统。 的 高胆固醇血症患者对乙酰胆碱的血管舒张反应受损， 与正常对照组相比， 对硝普钠的反应 基础血流量的减少 由L-NMMA产生的在高胆固醇血症和对照中是相似的。 作为 如前所述，L-NMMA显著减弱了对 乙酰胆碱在正常对照;然而，对乙酰胆碱的反应 L-NMMA对高血压患者的血压无明显影响。 这些发现 这表明内皮细胞基础一氧化氮产生不是 在高胆固醇血症患者中显著受损。 但 在刺激过程中一氧化氮的释放不足， 内皮依赖性血管扩张剂可能解释了异常的 这些患者的内皮介导的血管舒张。

Recent studies have demonstrated that the endothelium-dependent vascular relaxation of hypercholesterolemic animals and humans is impaired. We undertook the present investigation to determine the role of nitric oxide, one of the several factors produced by the endothelium, in this abnormal vasodilator response to endothelium-dependent agents. For this purpose, we studied the effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of the synthesis of nitric oxide by endothelial cells, on basal vascular tone and on the responses to acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (a smooth muscle dilator). Twenty hypercholesterolemic patients (plasma cholesterol > 240 mg/dl; age 49+8 years; 13 men and 7 women) and 18 normal controls (47+7 years; 11 men and 7 women). Drugs were given into the brachial artery and the response of the forearm vasculature was measured by strain guage plethysmography. The vasodilator response to acetylcholine was impaired in hypercholesterolemic patients compared to normal controls; however, no difference was found in the response to sodium nitroprusside. The reduction in basal blood flow produced by L-NMMA was similar in hypercholesterolemic and controls. As shown previously, L-NMMA significantly blunted the response to acetylcholine in normal controls; however, the response to acetylcholine was not modified by L-NMMA in hypertensive patients. These findings indicate that basal production of nitric oxide by endothelial cells is not significantly impaired in hypercholesterolemic patients. However, a deficit in the release of nitric oxide during stimulation with endothelium-dependent vasodilators may account for the abnormal endothelium mediated vasodilation of these patients.