Endothelin-1 induced contraction of rat aorta: contributions made by Ca2+ influx and activation of contractile apparatus associated with no change in cytoplasmic Ca2+ level.
The modes by which endothelin-1 (ET) induces Ca2(+)-influx and the relative functional importance of the different sources of Ca2+ for ET-induced contraction were studied using fura 2-loaded and unloaded rat aortic strips. ET caused an increase in the cytosolic free Ca2+ level ([Ca2+]i) followed by a tonic contraction in Ca2(+)-containing solution, and produced a transient elevation of [Ca2+]i followed by a small sustained contraction in Ca2(+)-free medium. ET also stimulated 45Ca influx into La3(+)-inaccessible fraction significantly. With the same change of [Ca2+]i, ET caused a larger tension than that induced by high K. ET-induced contraction and [Ca2+]i elevation were not significantly inhibited by 0.1-0.3 microM nicardipine which nearly abolished the contraction and [Ca2+]i elevation produced by high K. During treatment of the strips with high K, addition of ET induced further increases in [Ca2+]i and muscle tension, and vice versa. In Ca2(+)-free medium, ET-induced contraction was influenced neither by ryanodine-treatment nor by high K-treatment, although the former attenuated and the latter potentiated the [Ca2+]i transient induced by ET. Further, the ET-induced sustained contraction under Ca2(+)-free conditions began to develop after the [Ca2+]i level returned to the baseline. Thus, it seems that the Ca2+ released from the ryanodine-sensitive and -insensitive Ca2+ stores by ET may provide only a minor or indirect contribution, if any, to the tension development. ET might cause a contraction mainly by stimulating Ca2(+)-influx through Ca2+ channel(s) other than voltage-dependent Ca2+ channels in character, and by increasing the sensitivity of the contractile filaments to Ca2+ or activating them Ca2(+)-independently.
Huang
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Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Hisayama
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Takayanagi
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002132:Calcium Radioisotopes; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D016232:Endothelins; D016257:Fura-2; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology
D001572:Benzofurans; D002132:Calcium Radioisotopes; D016232:Endothelins; D010455:Peptides; D012433:Ryanodine; D009529:Nicardipine; D002118:Calcium; D016257:Fura-2