Endothelin in human congestive heart failure.

作者：Chao Wei, A. Lerman, Richard J. Rodeheffer, C G McGregor, Roland R. Brandt, Stephen P. Wright, Denise M. Heublein, Pei-Chun Kao, William D. Edwards, John C. Burnett · 发表于：Circulation · 年份：1994 · DOI：10.1161/01.cir.89.4.1580 · 被引用次数：589 · 研究领域：Nitric Oxide and Endothelin Effects、Cardiac Fibrosis and Remodeling、Pulmonary Hypertension Research and Treatments

BACKGROUND: Although recent investigations report the elevation of plasma endothelin (ET) in congestive heart failure (CHF), it remains unclear if this elevation is that of the biologically active peptide ET-1 or of its precursor big-ET. Furthermore, it is unclear if such elevation is associated with increased myocardial ET and if the molecular form from cardiac tissue is altered ET. Last, it remains to be established whether circulating ET is increased at the earliest stage of CHF in patients with asymptomatic left ventricular dysfunction and correlates with the magnitude of ventricular dysfunction. METHODS AND RESULTS: The present study was designed to investigate concentrations and molecular forms of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New York Heart Association (NYHA) class I through IV using cardiac radionuclide angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was increased only in patients with moderate (NYHA class III) or severe (NYHA class IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF showed a negative correlation with left ventricular ejection fraction and cardiac index and a positive correlation with functional class and left ventricular end-diastolic volume index. GPC demonstrated that immunoreactive plasma ET was ET-1 in heal...