Coronary vascular endothelial cells release substances into the corona
ry circulation that modify the contractile system of cardiac myocytes,
and cardiac myocytes may release factors that modulate the secretion
of cardioregulatory substances by endothelial cells. This regulatory l
oop is sensitive to the rate of coronary flow and tissue oxygen tensio
n. In the present study, coronary venous effluent from isolated perfus
ed hearts and the contents of the coronary vascular endothelial cells
have been collected, the latter by disrupting the cells with coronary
perfusion at high pressure. The relative amounts of upregulating and d
ownregulating factors in both collections have been estimated by assay
ing their effects on the contractility of isolated cardiac trabeculas.
The amount of upregulating factor stored in the endothelial cells is
sensitive to the rate of coronary flow just before disruption of the c
ells. The quantity of endothelin in the coronary venous effluent and i
n the vascular endothelial cell contents was measured by radioimmunoas
say and compared with the degree of upregulation of contractility prod
uced by the two types of solutions. Upregulation was never produced in
the absence of endothelin. The extent of the increase in contractilit
y that was observed with endothelial cell contents correlated with the
concentration of endothelin and was approximately the same as the inc
rease in contractility from similar concentrations of endothelin added
to standard Krebs' solution. The amount of the increase in contractil
ity from coronary effluent could be accounted for by the concentration
of endothelin in the effluent with the additional presence of some do
wnregulating factor as well. The endothelin antagonist BQ123 inhibited
the upregulation from coronary perfusate. It appears that endothelin
alone can account for all of the upregulation of contractility produce
d by the vascular endothelial cells. Coronary flow, probably through s
hear forces, seems to regulate the production of endothelin possibly f
rom an inactive precursor. Tissue oxygen tension appears to modulate t
he rate of release of the endothelin from endothelial cells though sub
stances released by cardiac myocytes or other cells in the tissue. The
downregulating factor is stored to a much smaller extent.