Ontkean M, Gay R, Greenberg B
Department of Internal Medicine, Oregon Health Sciences University, Portland 97201.
Circ Res. 1991 Oct;69(4):1088-96. doi: 10.1161/01.res.69.4.1088.
Abnormalities in vasomotor tone, including enhanced vasoconstriction at rest and diminished vasodilation in response to various stimuli, develop as a consequence of chronic heart failure. This study was undertaken to evaluate whether a specific local mechanism, namely endothelium-derived relaxing factor (EDRF) activity, might be impaired in an experimental model of chronic heart failure. Segments of thoracic aorta (TA) and pulmonary artery (PA) were isolated from a group of rats that had hemodynamic evidence of heart failure 10 weeks after ligation of the left coronary artery (n = 25) and from a group of sham-operated control rats (n = 18). Both endothelium-dependent and endothelium-independent vascular responses were assessed by exposing arterial segments to increasing concentrations of agonists. All studies were performed in the presence of 10 microM indomethacin to avoid the influence of vasoactive prostanoids. The dose-response curve for EDRF-mediated relaxation to acetylcholine was shifted rightward in rats with heart failure, and the concentrations of acetylcholine required to achieve 50% maximal relaxation (EC50) were increased compared with those of control rats in both TA and PA segments. Additionally, the dose-response curve for relaxation to ADP was shifted rightward with significantly increased EC50 in PA segments from rats with heart failure. In contrast, EDRF-mediated relaxation to the calcium ionophore A23187 was similar in the groups. Endothelium-independent relaxation to nitroglycerin was slightly increased in TA but not PA segments in the heart-failure group. Basal EDRF activity, as assessed by the increase in force after exposure to hemoglobin, was diminished in PA segments from rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
血管舒缩张力异常，包括静息时血管收缩增强以及对各种刺激的血管舒张减弱，是慢性心力衰竭的结果。本研究旨在评估在慢性心力衰竭的实验模型中，一种特定的局部机制，即内皮源性舒张因子（EDRF）活性是否可能受损。从一组在左冠状动脉结扎10周后有心力衰竭血流动力学证据的大鼠（n = 25）和一组假手术对照大鼠（n = 18）中分离出胸主动脉（TA）和肺动脉（PA）段。通过将动脉段暴露于浓度递增的激动剂来评估内皮依赖性和非内皮依赖性血管反应。所有研究均在10微摩尔吲哚美辛存在的情况下进行，以避免血管活性前列腺素的影响。心力衰竭大鼠中，EDRF介导的对乙酰胆碱舒张的剂量反应曲线向右移动，与对照大鼠相比，TA和PA段达到最大舒张50%所需的乙酰胆碱浓度（EC50）均增加。此外，心力衰竭大鼠PA段中，对ADP舒张的剂量反应曲线向右移动，EC50显著增加。相比之下，两组中EDRF介导的对钙离子载体A23187的舒张相似。心力衰竭组中，TA段而非PA段对硝酸甘油的非内皮依赖性舒张略有增加。通过暴露于血红蛋白后力量的增加评估的基础EDRF活性，在心力衰竭大鼠的PA段中降低。（摘要截断于250字）
