Pharmacological assessment of Ca2+ dependence of endothelin-1-induced response in rat aorta.
In rat aorta, endothelin-1 (ET-1) induced a slowly developing and sustained contraction in Ca(2+)-containing normal Krebs, nominally Ca(2+)-free Krebs, and Ca(2+)-free Krebs containing EGTA with a decreasing level of contraction. When ET-1-precontracted tissues were washed with Ca(2+)-free Krebs +50 microM EGTA, the tissues spontaneously and slowly relaxed. Readministration of Ca2+ during the early spontaneous relaxation phase caused a rapidly developing tonic contraction. When added during the late spontaneous relaxation phase, Ca2+ evoked slowly developing or, sometimes, biphasic contractions. In the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, the above biphasic contraction brought about by readministration of Ca2+ converted to a rapidly developing monophasic response. Thus, the first component of the biphasic contraction may be due to refilling of ET-1-sensitive Ca2+ store via the internal membrane Ca(2+)-pump. Furthermore, the ability of the phenylephrine-sensitive pool of internal Ca2+ to refill in the presence of 10(-8) M ET-1 suggests that the phenylephrine-sensitive pool differs from ET-1-sensitive pool and cannot be depleted by ET-1.
Shimamoto
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Department of Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, Ont., Canada.
Kwan
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CY
Daniel
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D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid; D016232:Endothelins / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007552:Isotonic Solutions; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016232:Endothelins; D007211:Indoles; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D010656:Phenylephrine; D004533:Egtazic Acid; D002118:Calcium; C000543:cyclopiazonic acid