The effect of extracellular calcium on the contractile action of endothelin.
The tension developed by rat aortic strips in response to endothelin-1 is determined by three types of mechanisms: a [Ca2+]o independent mechanism, L-type Ca2+ channels and a [Ca2+]o dependent, verapamil insensitive, mechanism. Their relative contributions to the tension recorded 30 minutes after the addition of 50 nM endothelin-1 were 43%, 34% and 23%. Upon longer exposures to endothelin-1, the whole tension could be abolished by reducing [Ca2+]o to 20 nM. Endothelin-1 induced contractions were highly sensitive to changes in free [Ca2+]o. The EC50 value for the [Ca2+]o dependence of endothelin-1 induced contractions was 600 nM, a value 400 times lower than the corresponding value found for KCl induced contractions (250 microM). These results suggest that extracellular Ca2+ is necessary for full tension development in response to endothelin-1 but that a major action of endothelin-1 is to increase the sensitivity of pharmacomechanical coupling mechanisms to Ca2+.
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Valbonne, France.
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R
Marsault
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P
Vigne
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C
Frelin
D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000494:pharmacology*; D016232:Endothelins; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D010455:Peptides; D011189:Potassium Chloride; D002118:Calcium