Endothelin (ET) is a potent vasoconstrictor peptide, released from endothel
ial cells, which is associated with prostaglandin (PG) release. The mechani
sm by which ET causes the release of PG is not clearly understood. We used
rat aortic endothelial cells to investigate the role of calcium (Ca2+) in E
T-1-induced prostacyclin (PGI(2)) release. ET-1 (10(-9) M) produced a signi
ficant increase in PGI(2) release. Pretreatment of rat aortic endothelial c
ells with different doses (10(-9) M and 10(-6) M) of diltiazem (voltage-sen
sitive L-type calcium channel blocker) produced significant inhibition of E
T-1- and PDBu-induced PGI(2) release. Inhibition was first noted at 10(-9)
M and was complete at 10(-6) M. Conversely, pretreatment of rat aortic endo
thelial cells with different doses (10(-9) M and 10(-6) M) of calcium chann
el blockers (thapsigargin, an intracellular calcium channel blocker or cono
toxin, a voltage-sensitive N-type calcium channel blocker) produced no chan
ges on ET-1- or PDBu-induced PGI(2) release. These results provide further
support for the concept that PKC mediates ET-induced PGI(2) release in rat
aortic endothelial cells via an increase in intracellular calcium and this
increase is due to the influx of extracellular calcium and not to the relea
se of calcium from the sarcoplasmic reticulum.