Original article| Volume 55, ISSUE 6, P413-417, December 1996

Role of calcium in endothelin-induced contractions and prostacyclin release

  • G.K. Oriji
    Correspondence to: Dr. Gibson K. Oriji, Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, Bldg 10, Room 8C103, 10 Center Drive, MSC 1754, Bethesda, MD 20892-1754; Tel. (301) 496-9555; Fax. (301) 402-1679.
    Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 USA
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  • H.R. Keiser
    Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 USA
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      Endothelin-1 (ET-1) is a potent vasoconstrictor peptide that induces characteristically long-lasting contractions. We used rat aortic rings to investigate the role of protein kinase C (PKC) in ET-1-induced contractions and prostacyclin (PGI2) 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 diltiazem (voltage-sensitive L-type calcium channel blocker) produced significant inhibition of ET-1- and PDBu-induced contractions and PGI2 release. Inhibition was first noted at 10−9 M and was complete at 10−6 M. Conversely, pretreatment of aortic rings with different doses (10−9 M and 10−6 M) of calcium channel blockers (thapsigargin, an intracellular calcium channel blocker, or conotoxin, a voltage-sensitive N-type calcium channel blocker) produced no changes on ET-1- or PDBu-induced contraction or PGI2 release. These results provide further support for the concept that PKC mediates ET-induced contractions and PGI2 release in rat aortic rings via an increase in intracellular calcium and this increase is due to the influx of extracellular calcium and not to the release of calcium from the sarcoplasmic reticulum.
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