1. Endocardial expression and functional characterization of endothelin-1
- Author
-
O, Saetrum Opgaard, M, Adner, T H, Peters, C B, Xu, L, Stavenow, S, Gulbenkian, D, Erlinge, L, Edvinsson, and H S, Sharma
- Subjects
Endothelin-3 ,Endothelin-1 ,Receptors, Endothelin ,Reverse Transcriptase Polymerase Chain Reaction ,Receptor, Endothelin A ,Receptor, Endothelin B ,Rats ,Culture Media, Conditioned ,Animals ,Humans ,RNA, Messenger ,Aorta ,Cells, Cultured ,Endocardium ,Muscle Contraction - Abstract
Endothelin-1 (ET-1), a 21 amino acid peptide exerts a wide range of biological activities including vasoconstriction, mitogenesis and inotropic effects on the heart. In this study, we examined whether endocardial endothelial cells express ET-1 and evaluated its functional properties. Using immunofluorescence 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-PCR) expression of ET-1 mRNA and its receptors ET(A) and ET(B) mRNAs were found in human myocardial as well as in endocardial endothelial cells. Biological activity of endocardial endothelial cells derived ET-1 was established as the 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 antagonist, FR 139317, blocked the conditioned media induced contractions. Our results suggest that endocardial endothelial cells express and release biologically active ET-1 which could play a pivotal role in the regulation of myocardial contractility as well as a circulatory peptide may further act in other peripheral target organs.
- Published
- 2001