Hemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure
Hemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure
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DOI：
10.1161/01.cir.101.23.2764
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发表时间：
2000-06-13
期刊：
影响因子：
37.8
通讯作者：
Michel, JB
中科院分区：
文献类型：
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作者：
Ben Driss, A;Devaux, C;Michel, JB
背景-我们假设，在代偿性心力衰竭(HF)中，尽管胸主动脉(TA)没有任何扰动，但存在肺动脉(PA)的血流动力学扰动及其后果。方法和结果：20只雄性Wistar大鼠在代偿性心力衰竭(HF)时结扎左冠状动脉。结扎4个月后，将这些大鼠与20只假手术对照组大鼠进行比较。测量PA和TA的血压、血流速度、粘度、管腔直径、室壁拉应力和剪应力。动脉环安装在肌图仪上，用于体外研究。检测肺和主动脉组织内皮型一氧化氮合酶(ENOS)mRNA的表达。用PA和TA切片进行组织形态计量学研究。在代偿性心力衰竭大鼠，(1)血压和室壁张应力增加，而血流速度和室壁切应力降低；(2)对KCl的收缩没有改变，但对苯肾上腺素和EC50的最大收缩降低；(3)对乙酰胆碱的内皮依赖性松弛和基础NO活性减弱，而非内皮非依赖性NT松弛被保留；(4)肺细胞核eNOS mRNA水平和eNOS转录水平下降；(5)内膜横截面积、厚度、平滑肌细胞数量、弹性蛋白和胶原含量增加。结论小心肌梗死后代偿性心衰大鼠的心功能、血流动力学、血管壁功能和结构均发生改变，而TA则保持不变。这些结果表明，肺血管床是心力衰竭局部循环改变的早期靶点。
Background-We hypothesized that, in compensated heart failure (HF), hemodynamic perturbations and their consequences exist in pulmonary artery (PA) despite the absence of any perturbation in thoracic aorta (TA).Methods and Results-The left coronary artery was ligated in 20 male Wistar rats with compensated HF. Four months after ligation, these rats were compared with 20 sham-operated control rats. Blood pressure, velocity, viscosity, luminal diameter, and wall tensile and shear stresses were determined in PA and TA. Arterial rings were mounted in a myograph for ex vivo study. Endothelial nitric oxide synthase (eNOS) mRNA expression was determined in lung and aorta. Sections of PA and TA were used for histomorphometric study. In PA from rats with compensated HF, (1) blood pressure and wall tensile stress increased, whereas blood velocity and wall shear stress decreased; (2) contractions to KCl were not altered, but maximal contraction to phenylephrine and EC50 decreased; (3) endothelium-dependent relaxation to acetylcholine and basal NO activity were blunted, whereas endothelium-independent nt relaxation was preserved; (4) eNOS mRNA levels and eNOS transcription in lung nuclei decreased; and (5) medial cross-sectional area, thickness, smooth muscle cell number, elastin, and collagen contents increased. Conversely, no such changes were found in TA from rats with compensated HF.Conclusions-In compensated HF induced by small myocardial infarction, hemodynamics, vascular wall function, and structure are altered in PA but preserved in TA. These results indicate that the pulmonary vascular bed is an early target of regional circulatory alterations in HF.