Endothelin-1, endothelin-1 receptors and cardiac natriuretic peptides in failing human heart

Endothelin (ET)-1 is a potent vasoconstrictor peptide produced in the myoca rdium that can exert important effects on cardiac myocyte growth and phenot ype; cardiac natriuretic peptides (ANP and BNP) are known to act as physiol ogical antagonists of ET-1. In this study a comparative determination of ET -1 receptors and of the local productions of ET-1 and of ANP and BNP was ma de in different sites of failing and nonfailing hearts. Tissue from right a nd left atrium, right and left ventricle and interventricular septum from s even adult heart transplant recipients with end-stage idiopathic dilated ca rdiomyopathy (functional class m and TV, with ejection fraction < 35%) and from four post-mortem subjects without cardiac complications was analyzed. In failing hearts we observed a tendency to increase of density of binding sites, most evident in left ventricle (62.6 +/- 22.6 fmol/mg protein vs. 29 .0 +/- 3.3, mean +/- SEM, p ns). A prevalence of ET-A subclass, observed in all samples, resulted more pronounced in failing hearts where this increas e, found in all the cardiac regions, was more evident in left ventricle (p = 0.0007 vs nonfailing hearts). The local concentrations of ET-1, ANP and B NP resulted significantly increased in failing hearts with respect to contr ols in all sides of the heart. In failing hearts we have observed a tendenc y to increase in endothelin receptor density mainly due to a significant up regulation of ET-A subtype and a parallel increase of the tissue levels of ANP, BNP and ET-1 indicating an activation of these systems in heart failur e. (C) 2001 Elsevier Science Inc. All rights reserved.