ROLE OF CALCIUM IN ENDOTHELIN-INDUCED CONTRACTIONS AND PROSTACYCLIN RELEASE

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that induces c haracteristically long-lasting contractions. We used rat aortic rings to investigate the role of protein kinase C (PKC) in ET-1-induced cont ractions and prostacyclin (PGI(2)) release. ET-(1) (10(-9) M) produced a gradual and sustained contraction in rat aortic rings. Pretreatment of aortic rings with different doses (10(-9) M and 10(-6) M) of dilti azem (voltage-sensitive L-type calcium channel blocker) produced signi ficant inhibition of ET-1- and PDBu-induced contractions and PGI(2) re lease. Inhibition was first noted at 10(-9) M and was complete at 10(- 6) M. Conversely, pretreatment of aortic rings with different doses (1 0(-9) M and 10(-6) M) of calcium channel blockers (thapsigargin, an in tracellular calcium channel blocker, or conotoxin, a voltage-sensitive N-type calcium channel blocker) produced no changes on ET-1- or PDBu- induced contraction or PGI(2) release. These results provide further s upport for the concept that PKC mediates ET-induced contractions and P GI(2) release in rat aortic rings via an increase in intracellular cal cium and this increase is due to the influx of extracellular calcium a nd not to the release of calcium from the sarcoplasmic reticulum.