ENDOTHELIN-1 RELEASE FROM ENDOTHELIAL-CELLS IN CULTURE IS ELEVATED BOTH ACUTELY AND CHRONICALLY BY SHORT PERIODS OF MECHANICAL STRETCH

The effects were examined of mechanical stretch on the release of endothelin-1 (ET-1) and prostacyclin (measured as 6-keto-prostaglandin (PG) F-1 alpha) from cultured endothelial cells. Stretching (0.2 Hz) for 20, 60 or 360 min caused immediate (less than or equal to 20 min) and secondary (up to 360 min) increases in ET-1 release. The secondary but not immediate release of ET-1 was prevented by actinomycin D (8 x 10(-7) M) or cycloheximide (3.6 x 10(-6) M). Neither compound affected the release of ET-1 from unstretched cells over 360 min. Stretching of the endothelial cells increased the accumulation of 6-keto-PGF(1 alpha) at 360 min but not at 20 min, suggesting that stretch does not produce a rapid, non-selective increase in autacoid production from endothelial cells. The intracellular amounts of ET-1 were approximately 20 times greater than those of big ET-1. Thus, endothelial cells contain stores of ET-1 that are released rapidly by stretch. (C) 1994 Academic Press, Inc.