Dupuis J, Rouleau J L, Cernacek P
Department of Medicine, Montreal Heart Institute, Montreal, Quebec, Canada.
Circulation. 1998 Oct 20;98(16):1684-7. doi: 10.1161/01.cir.98.16.1684.
The pulmonary vascular bed is a major site for endothelin-1 (ET-1) clearance. A reduced clearance could contribute to the increase in circulating ET-1 levels found in heart failure (HF). We therefore evaluated the effect of HF on pulmonary ET-1 clearance and on plasma ET-1 concentrations.
Rats with myocardial infarction (n=24) were compared with sham-operated rats (n=22). The lungs were isolated and perfused at a constant flow rate of 10 mL/min. Pulmonary ET-1 clearance was measured by the single-bolus indicator-dilution technique with 125I-labeled ET-1. Infarct rats developed HF with mild pulmonary hypertension. ET-1 extraction was reduced by HF from 63+/-1.5% to 41+/-4.5% (mean+/-SEM, P<0.001). Mixed venous (MV) and aortic ET-1 levels doubled with HF. There was a plasma ET-1 gradient across the lungs of sham rats (MV-aortic levels, 0.21+/-0.12 pg/mL) but not in lungs of HF rats (0.01+/-0.17 pg/mL). Plasma ET-1 levels correlated closely and inversely with ET-1 extraction (P<0.001).
HF is associated with reduced pulmonary ET-1 clearance that contributes to the increase in circulating levels.
肺血管床是内皮素-1（ET-1）清除的主要部位。清除率降低可能导致心力衰竭（HF）时循环中ET-1水平升高。因此，我们评估了HF对肺ET-1清除率和血浆ET-1浓度的影响。
将心肌梗死大鼠（n=24）与假手术大鼠（n=22）进行比较。分离肺并以10 mL/min的恒定流速进行灌注。采用单剂量指示剂稀释技术，用125I标记的ET-1测量肺ET-1清除率。梗死大鼠发生HF并伴有轻度肺动脉高压。HF使ET-1提取率从63±1.5%降至41±4.5%（均值±标准误，P<0.001）。HF时混合静脉（MV）和主动脉ET-1水平加倍。假手术大鼠肺内存在血浆ET-1梯度（MV-主动脉水平，0.21±0.12 pg/mL），而HF大鼠肺内不存在（0.01±0.17 pg/mL）。血浆ET-1水平与ET-1提取率密切负相关（P<0.001）。
HF与肺ET-1清除率降低有关，这导致了循环水平的升高。
