Negrao C E, Hamilton M A, Fonarow G C, Hage A, Moriguchi J D, Middlekauff H R
Laboratory of Cardiovascular Physiology in Exercise, Heart Institute, University of Sao Paulo, School of Medicine, Sao Paulo, 05403-000, Brazil.
Am J Physiol Heart Circ Physiol. 2000 Jan;278(1):H168-74. doi: 10.1152/ajpheart.2000.278.1.H168.
The extent to which abnormal endothelium-dependent vasodilator mechanisms contribute to abnormal resting vasoconstriction and blunted reflex vasodilation seen in heart failure is unknown. The purpose of this study was to test the hypothesis that the resting and reflex abnormalities in vascular tone that characterize heart failure are mediated by abnormal endothelium-mediated mechanisms. Thirteen advanced heart-failure patients (New York Heart Association III-IV) and 13 age-matched normal controls were studied. Saline, acetylcholine (20 microg/min), or L-arginine (10 mg/min) was infused into the brachial artery, and forearm blood flow was measured by venous plethysmography at rest and during mental stress. At rest, acetylcholine decreased forearm vascular resistance in normal subjects, but this response was blunted in heart failure. During mental stress with intra-arterial acetylcholine or L-arginine, the decrease in forearm vascular resistance was not greater than during saline control in heart failure [saline control vs. acetylcholine (7 +/- 3 vs. 6 +/- 3, P = NS) or vs. L-arginine (9 +/- 2 units, P = NS)]. The increase in forearm blood flow was not greater than during saline control in heart failure [saline control vs. acetylcholine (1. 2 +/- 0.3 vs. 1.3 +/- 0.3, P = NS), or vs. L-arginine (1.2 +/- 0.2 ml x min(-1) x 100 ml(-1), P = NS)]. Furthermore, during mental stress with nitroprusside, the decrease in forearm vascular resistance was not greater than during saline control [saline control vs. nitroprusside (7 +/- 3 vs. 5 +/- 4 ml x min(-1) x 100 g(-1), P = NS)], and the increase in forearm blood flow was not greater than during saline control [saline control vs. nitroprusside (1.2 +/- 0.3 vs. 1.3 +/- 0.5 ml x min(-1) x 100 g(-1), P = NS)]. Because the endothelial-independent agent nitroprusside was unable to restore resting and reflex vasodilation to normal in heart failure, we conclude that impaired endothelium-mediated vasodilation with acetylholine-nitric oxide cannot be the principal cause of the attenuated resting- or reflex-mediated vasodilation in heart failure.
异常的内皮依赖性血管舒张机制在多大程度上导致心力衰竭时出现的静息性血管收缩异常和反射性血管舒张减弱尚不清楚。本研究的目的是检验以下假设：心力衰竭时特征性的血管张力静息和反射异常是由异常的内皮介导机制介导的。研究了13例晚期心力衰竭患者（纽约心脏协会III-IV级）和13例年龄匹配的正常对照者。将生理盐水、乙酰胆碱（20微克/分钟）或L-精氨酸（10毫克/分钟）注入肱动脉，在静息和精神应激期间通过静脉体积描记法测量前臂血流量。静息时，乙酰胆碱可降低正常受试者的前臂血管阻力，但这种反应在心力衰竭患者中减弱。在精神应激期间，给予动脉内乙酰胆碱或L-精氨酸时，心力衰竭患者前臂血管阻力的降低幅度不大于生理盐水对照期间[生理盐水对照与乙酰胆碱（7±3对6±3，P=无显著性差异）或与L-精氨酸（9±2单位，P=无显著性差异）]。心力衰竭患者前臂血流量的增加幅度不大于生理盐水对照期间[生理盐水对照与乙酰胆碱（1.2±0.3对1.3±0.3，P=无显著性差异），或与L-精氨酸（1.2±0.2毫升·分钟-1·100毫升-1，P=无显著性差异）]。此外，在精神应激期间给予硝普钠时，心力衰竭患者前臂血管阻力的降低幅度不大于生理盐水对照期间[生理盐水对照与硝普钠（7±3对5±4毫升·分钟-1·100克-1，P=无显著性差异）]，前臂血流量的增加幅度不大于生理盐水对照期间[生理盐水对照与硝普钠（1.2±0.3对1.3±0.5毫升·分钟-1·100克-1，P=无显著性差异）]。由于不依赖内皮的药物硝普钠无法使心力衰竭患者的静息和反射性血管舒张恢复正常，我们得出结论，乙酰胆碱-一氧化氮介导的内皮依赖性血管舒张受损不是心力衰竭时静息或反射介导的血管舒张减弱的主要原因。
