Role of sarcoplasmic reticulum in the contractile function of vascular smooth muscle as studied by 2,5-di-(tert-butyl)-1,4-benzohydroquinone.
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The effects of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent selective inhibitor of hepatocyte endoplasmic reticulum Ca(2+)-ATPase, were functionally examined in rat aorta in order to assess whether tBuBHQ also acts as a Ca2+ pump inhibitor of sarcoplasmic reticulum (SR) in vascular smooth muscle. tBuBHQ elicited a slowly developing and gradually decreasing contraction which was dependent on extracellular Ca2+. We utilize the phenylephrine (PE)-induced transient contractile response in Ca(2+)-free medium as an indirect index on the status of intracellular Ca2+ store. When preparations, depleted of their PE-sensitive Ca2+ store, were allowed to replete their stores in Ca(2+)-containing medium, a sustained contraction in tBuBHQ-treated preparations was observed, whereas in untreated control preparations, readministration of Ca2+ elicited no contraction, or occasionally a weak, transient contraction. In control tissues, subsequent application of PE in Ca(2+)-free medium after Ca2+ loading resulted in full restoration of the transient contraction to PE; but such a transient contraction was not observed in the presence of tBuBHQ. These results indicated that the sequestration of Ca2+ into the PE-sensitive pool was inhibited by tBuBHQ. We also assessed effects of tBuBHQ on phentolamine-induced relaxation in PE-precontracted tissues in Ca(2+)-containing medium. A slower rate of relaxation was observed in preparations treated with tBuBHQ. In conclusion, our findings are consistent with the hypothesis that tBuBHQ acts as a SR Ca2+ pump inhibitor, interfering with effective refilling of PE-sensitive intracellular Ca2+ stores.
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