PARACRINE EFFECTS OF ENDOCARDIAL ENDOTHELIAL-CELLS ON MYOCYTE CONTRACTION MEDIATED VIA ENDOTHELIN

Endocardial endothelium is reported to modulate myocardial contraction by releasing diffusible factors, but the nature of the agent(s) respo nsible is unknown. In the present study we investigated the potential role of endothelin in these effects. Cultured sheep endocardial endoth elial cells were found to express endothelin-1 mRNA and to release end othelin-1 into superfusing solution. This superfusate induced positive inotropic effects in isolated rat cardiac myocytes, associated with a n increase in the cytosolic Ca2+ transient. Similar positive inotropic effects were induced by vascular endothelial cell superfusate as well as by synthesized endothelin-1, administered at concentrations simila r to those present in the superfusate. Incubation of endocardial endot helial cell superfusate with endothelin-1-specific antiserum reduced t he free endothelin-1 concentration to undetectable levels and abolishe d both the positive inotropic effect and the rise in cytosolic Ca2+. T hese findings indicate that endocardial endothelial cells may modulate myocardial contraction in part through the release of endothelin-1 an d suggest that endocardial as well as vascular endothelium could exert potent paracrine effects on myocardium.