THE PRODUCTION OF CORONARY VASOCONSTRICTOR SUBSTANCES BY FRESHLY HARVESTED ENDOTHELIAL-CELLS

The effects of cell free superfusates from freshly harvested bovine endothelial cells attached to microcarrier beads on the isolated rabbit and rat heart and on superfused rabbit jugular veins were observed. Cell free conditioned filtrates from freshly harvested cells caused marked diminution in coronary flow and cardiac output in the isolated rabbit heart; in the perfused rat heart an increase in coronary perfusion pressure and a decline in left ventricular systolic tension and maximal left ventricular contractility (dP/dt) were recorded. Marked differences were found between changes induced by conditioned filtrate as compared to synthetic endothelin. Endothelin as present in conditioned filtrate could not account for the pronounced effect on coronary perfusion pressure, dp/dt and cardiac output induced by conditioned filtrate; more than one hundred times that of synthetic endothelin was needed to achieve comparable cardiodynamic effects. This suggested that additional non-prostanoid vasoconstrictor substance or substances are produced by freshly harvested endothelial cells. This conclusion was supported by the observation that BQ-123, a specific inhibitor of endothelin A (ET(A)) receptor significantly prevented contractions by endothelin, while failing to inhibit those induced by freshly harvested endothelial cells. These constrictor substances may be