Role of calcium in endothelin-induced contractions and prostacyclin release.
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.
Oriji
G K
GK
Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Keiser
H R
HR
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D019332:Endothelin-1; D015240:Phorbol 12,13-Dibutyrate; D019284:Thapsigargin; D011464:Epoprostenol; D011493:Protein Kinase C; D004110:Diltiazem; D002118:Calcium