NITRIC OXIDE IN ENDOTHELIUM-DEPENDENT VASODILATION IN HYPERCHOLESTEROLEMIA

高胆固醇血症中内皮依赖性血管舒张中的一氧化氮

• 批准号: 3843419
• 负责人: J A PANZA
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3843419
• 关键词: acetylcholine; aminoacid analog; arginine; blood flow measurement; cardiovascular pharmacology; human subject; hypercholesterolemia; intraarterial administration; nitric oxide; nitroferricyanide; plethysmography; vascular endothelium; vascular smooth muscle; vasodilation; vasodilators

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.

最近的研究表明，内皮依赖性血管 高胆固醇血症动物和人类的松弛功能受损。我们 进行了本次调查，以确定一氧化氮的作用， 内皮细胞产生的几个因素之一，在这种异常情况下 血管扩张剂对内皮依赖性药物的反应。为此， 我们研究了抑制剂L-精氨酸(NMMA)的作用 在基底血管内皮细胞合成一氧化氮 张力和对乙酰胆碱(内皮依赖性)的反应 血管扩张剂)和硝普钠(一种血管扩张剂)。二十 高胆固醇血症患者(血浆胆固醇240 mg/dl；年龄49±8岁) 18名正常对照(47+7岁；11名男性和7名女性)。 7名女性)。将药物注入臂动脉，对患者的反应 应用应变片体积描记仪测量前臂血管构型。这个 高胆固醇血症患者对乙酰胆碱的血管扩张反应受损 患者与正常对照组进行比较；然而，在 对硝普钠的反应。基础血流量减少 L-NMMA生产的药物在高胆固醇血症和对照组中的作用相似。AS 如前所述，L-NMMA显著钝化了对 正常对照组的乙酰胆碱；然而，对乙酰胆碱的反应 高血压病患者未经L-尼莫地平修饰。这些发现 表明内皮细胞基础产生的一氧化氮不是 在高胆固醇血症患者中显著受损。然而，a 刺激过程中一氧化氮释放不足 内皮依赖性血管扩张剂可能是异常的原因 血管内皮细胞介导的血管扩张。