Casino P R, Kilcoyne C M, Cannon R O, Quyyumi A A, Panza J A
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Am J Cardiol. 1995 Jan 1;75(1):40-4. doi: 10.1016/s0002-9149(99)80524-4.
Patients with hypercholesterolemia have impaired endothelium-dependent vasodilation. However, previous human studies have invariably used muscarinic agents to assess endothelial function. The purpose of this investigation was to determine whether impaired endothelium-dependent vasodilation of hypercholesterolemic patients is related to a specific and isolated defect of the muscarinic receptor, or to a broader abnormality of the endothelial cells. The forearm vascular responses to the endothelium-dependent agents acetylcholine (7.5, 15, and 30 micrograms/min) and substance P (1, 2, and 4 pmol/min), and to the direct smooth muscle dilator sodium nitroprusside (0.8, 1.6, and 3.2 micrograms/min) were studied in 16 hypercholesterolemic patients (8 men and 8 women; age [mean +/- SD] 50 +/- 7 years; serum cholesterol > 250 mg/dl) and 16 normal volunteers (8 men and 8 women; age 47 +/- 8 years; serum cholesterol < 200 mg/dl). Drugs were infused into the brachial artery and the response of the forearm vasculature was measured by strain-gauge plethysmography. The vasodilator response to acetylcholine was reduced in hypercholesterolemic patients compared with normal controls; at the highest dose (30 micrograms/min) the increase in forearm blood flow was 13.5 +/- 7 ml/min/100 ml in controls and 7.54 +/- 6 in patients (p < 0.05). The response to substance P was also blunted in hypercholesterolemic patients; at the highest dose (4 pmol/min), the increase in forearm blood flow was 12.1 +/- 5 ml/min/100 ml in controls and 7.6 +/- 4 in patients (p < 0.03). A significant correlation was found between the highest blood flow responses with acetylcholine and with substance P (r = 0.58; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
高胆固醇血症患者存在内皮依赖性血管舒张功能受损。然而，既往人体研究一直使用毒蕈碱类药物来评估内皮功能。本研究的目的是确定高胆固醇血症患者内皮依赖性血管舒张功能受损是与毒蕈碱受体的特定孤立缺陷有关，还是与内皮细胞的更广泛异常有关。对16例高胆固醇血症患者（8例男性和8例女性；年龄[均值±标准差]50±7岁；血清胆固醇>250mg/dl）和16名正常志愿者（8例男性和8例女性；年龄47±8岁；血清胆固醇<200mg/dl）的前臂血管对内皮依赖性药物乙酰胆碱（7.5、15和30微克/分钟）和P物质（1、2和4皮摩尔/分钟）以及对直接平滑肌扩张剂硝普钠（0.8、1.6和3.2微克/分钟）的反应进行了研究。将药物注入肱动脉，通过应变片体积描记法测量前臂血管系统的反应。与正常对照组相比，高胆固醇血症患者对乙酰胆碱的血管舒张反应降低；在最高剂量（30微克/分钟）时，对照组前臂血流增加为13.5±7毫升/分钟/100毫升，患者为7.54±6毫升/分钟/100毫升（p<0.05）。高胆固醇血症患者对P物质的反应也减弱；在最高剂量（4皮摩尔/分钟）时，对照组前臂血流增加为12.1±5毫升/分钟/100毫升，患者为7.6±4毫升/分钟/100毫升（p<0.03）。发现乙酰胆碱和P物质的最高血流反应之间存在显著相关性（r=0.58；p<0.001）。（摘要截断于250字）
