Endothelin in human congestive heart failure.

Abstract

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 healthy subjects and both mature ET-1 and its precursor big-ET in severe CHF patients, with big-ET the predominant molecular form. Cardiac tissue concentrations and IHCS revealed ET presence in healthy atrial and ventricular tissue, which were not different in severe CHF. GPC revealed that the molecular form of cardiac ET was ET-1 in both healthy and CHF hearts. CONCLUSIONS The present study establishes for the first time that the elevation of plasma ET in severe human CHF represents principally elevation of big-ET. Second, ET is present in healthy and failing myocardia, and its activity by both immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild CHF. In addition, the degree of plasma elevation of ET correlates with the magnitude of alterations in cardiac hemodynamics and functional class. The present study confirms and extends previous investigations of ET in human CHF and establishes the evolution of circulating and local cardiac ET in the spectrum of human CHF.

Increased renal formation of thromboxane A 2 and prostaglandin F 2α in heart failure

“…Likewise, plasma endothelin concentration in patients with CHF has been shown to be closely related to pulmonary artery pressure values. 28 In our study, PRA was significantly increased only in class IV patients. Our observations confirm and extend the findings of others who have shown that angiotensin activity is increased only in the more advanced phases of heart disease.…”

Why do patients with heart failure suffer from erectile dysfunction? A critical review and suggestions on how to approach this problem

“…Heart failure is associated with increased circulating vasoconstrictors such as endothelin (ET), 41,42 as well as a reduction in vasodilators such as prostacyclin. 43 ET-1 potently induces slowly developing, long-lasting contractions in the CC and penile vessels, and has been suggested to contribute to the maintenance of corpus cavernosal smooth muscle tone.…”

Modulation of Circulating Endothelin-1 and Big Endothelin by Nitric Oxide Inhalation Following Left Ventricular Assist Device Implantation

“…3,18 An aggravation of pulmonary hypertension during and after CPB, among other reasons, has been explained by CPB induced endothelial dysfunction. 19 A decrease of the basal endothelial NO release has been discussed as one possible explanation.…”