Kubo S H, Rector T S, Bank A J, Williams R E, Heifetz S M
Cardiovascular Division, University of Minnesota, Minneapolis 55455.
Circulation. 1991 Oct;84(4):1589-96. doi: 10.1161/01.cir.84.4.1589.
Endothelial cells produce a number of substances, collectively termed endothelium-derived relaxing factor (EDRF), that promote local relaxation of vascular smooth muscle. Although studies have demonstrated defects in endothelium-dependent vasodilation in animal models of hypertension, atherosclerosis, and heart failure, there are only limited data from human subjects because of the difficulty in obtaining fresh vascular segments.
To address the hypothesis that endothelium-dependent vasodilation is attenuated in patients with heart failure, we measured forearm blood flow responses to the intra-arterial administration of methacholine, a known stimulus of EDRF release through muscarinic receptors. In 14 normal subjects, a dosage range of methacholine increased forearm blood flow by 5.26 +/- 0.63, 10.50 +/- 0.63, and 13.22 +/- 0.86 ml/min/100 ml forearm volume (FAV); these responses were 1.98 +/- 0.46, 5.48 +/- 0.79, and 8.50 +/- 1.53 ml/min/100 ml FAV in 14 patients with heart failure. When pooled over all doses, the responses were strikingly less in the patients with heart failure (5.32 +/- 0.31 versus 9.52 +/- 0.60 ml/min/100 ml FAV; p = 0.0003). In a second study, the average difference in forearm blood flow responses between patients with heart failure and normal subjects with methacholine was significantly greater than the average difference between the groups with nitroprusside (4.04 +/- 1.10 versus 2.20 +/- 0.71 ml/min/100 ml FAV; p = 0.04). The decreased methacholine responses in the patients with heart failure were not related to age (r = 0.39; p = NS) or etiology because there was no difference in the responses between patients with ischemic heart disease and those with idiopathic cardiomyopathy.
These data suggest that endothelium-dependent vasodilation is attenuated in patients with heart failure. Although the mechanisms of the decreased endothelium-dependent responses in heart failure are not known, this impaired local vasodilation may contribute to abnormalities in vasoconstriction that are characteristic of heart failure.
内皮细胞产生多种物质，统称为内皮源性舒张因子（EDRF），可促进血管平滑肌局部舒张。尽管研究已在高血压、动脉粥样硬化和心力衰竭的动物模型中证实了内皮依赖性血管舒张存在缺陷，但由于获取新鲜血管段存在困难，来自人体受试者的数据有限。
为验证心力衰竭患者内皮依赖性血管舒张减弱这一假说，我们测量了前臂血流对动脉内注射乙酰甲胆碱的反应，乙酰甲胆碱是一种已知的通过毒蕈碱受体释放EDRF的刺激物。在14名正常受试者中，不同剂量的乙酰甲胆碱使前臂血流分别增加5.26±0.63、10.50±0.63和13.22±0.86 ml/分钟/100 ml前臂容积（FAV）；在14名心力衰竭患者中，这些反应分别为1.98±0.46、5.48±0.79和8.50±1.53 ml/分钟/100 ml FAV。汇总所有剂量的数据后，心力衰竭患者的反应明显较低（5.32±0.31与9.52±0.60 ml/分钟/100 ml FAV；p = 0.0003）。在第二项研究中，心力衰竭患者与正常受试者对乙酰甲胆碱的前臂血流反应平均差异显著大于对硝普钠的两组间平均差异（4.04±1.10与2.20±0.71 ml/分钟/100 ml FAV；p = 0.04）。心力衰竭患者乙酰甲胆碱反应降低与年龄（r = 0.39；p = 无显著性差异）或病因无关，因为缺血性心脏病患者与特发性心肌病患者的反应无差异。
这些数据表明心力衰竭患者内皮依赖性血管舒张减弱。尽管心力衰竭时内皮依赖性反应降低的机制尚不清楚，但这种局部血管舒张受损可能导致心力衰竭特有的血管收缩异常。
