Endocardial expression and functional characterization of endothelin-1

Endothelin-1 (ET-1), a 21 amino acid peptide exerts a wide range of biologi cal activities including vasoconstriction, mitogenesis and inotropic effect s on the heart. In this study, we examined whether endocardial endothelial cells express ET-1 and evaluated its functional properties. Using immunoflu orescence localization method, we demonstrated cytoplasmic staining of ET-1 in the human endocardial endothelial cells from the right atrium and left ventricle. Employing reverse transcriptase polymerase chain reaction (RT-PC R) expression of ET-1 mRNA and its receptors ETA and ETB mRNAs were found i n human myocardial as well as in endocardial endothelial cells. Biological activity of endocardial endothelial cells derived ET-1 was established as t he conditioned media obtained from cultured porcine endocardial endothelial cells induced a slowly developing, strong and long-lasting contraction of circular rat aortic segments, with similar characteristics to that obtained with exogenous ET-1. Furthermore, the selective endothelin-A receptor anta gonist, FR139317, blocked the conditioned media induced contractions. Our r esults suggest that endocardial endothelial cells express and release biolo gically active ET-1 which could play a pivotal role in the regulation of my ocardial contractility as well as a circulatory peptide may further act in other peripheral target organs.