Endothelin-induced prostacyclin production in rat aortic endothelial cells: role of calcium

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.