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) F1 alpha) from cultured endothelial cells. Stretching (0.2 Hz) for 20, 60 or 360 min caused immediate (< or = 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-PGF1 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.
Macarthur
H
H
William Harvey Research Institute, Medical College, St. Bartholomew's Hospital, London, U.K.
Warner
T D
TD
Wood
E G
EG
Corder
R
R
Vane
J R
JR
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism; D007700:Kinetics; D011498:Protein Precursors / Q000096:biosynthesis; D013314:Stress, Mechanical; D013997:Time Factors
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D003609:Dactinomycin; D015121:6-Ketoprostaglandin F1 alpha; D003513:Cycloheximide; D011464:Epoprostenol