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Role of Sarcoplasmic Reticulum in the Contractile Function of Vascular Smooth Muscle as Studied by 2,5-Di-(Tert-Butyl)-1,4-Benzohydroquinone

Role of Sarcoplasmic Reticulum in the Contractile Function of Vascular Smooth Muscle as Studied... The effects of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent selective inhibitor of hepatocyte endoplasmic reticulum Ca<sup>2+</sup>-ATPase, were functionally examined in rat aorta in order to assess whether tBuBHQ also acts as a Ca<sup>2+</sup> pump inhibitor of sarcoplasmic reticulum (SR) in vascular smooth muscle. tBuBHQ elicited a slowly developing and gradually decreasing contraction which was dependent on extracellular Ca<sup>2+</sup>. We utilize the phenylephrine (PE)-induced transient contractile response in Ca<sup>2+</sup>-free medium as an indirect index on the status of intracellular Ca<sup>2+</sup> store. When preparations, depleted of their PE-sensitive Ca<sup>2+</sup> store, were allowed to replete their stores in Ca<sup>2+</sup>-containing medium, a sustained contraction in tBuBHQ-treated preparations was observed, whereas in untreated control preparations, readministration of Ca<sup>2+</sup> elicited no contraction, or occasionally a weak, transient contraction. In control tissues subsequent application of PE in Ca<sup>2+</sup>-free medium after Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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<sup>2+</sup>-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 Ca<sup>2+</sup> pump inhibitor, interfering with effective refilling of PE-sensitive intracellular Ca<sup>2+</sup> stores. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosignals Karger

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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Publisher
Karger
Copyright
© 1992 S. Karger AG, Basel
ISSN
1424-862X
eISSN
1424-8638
DOI
10.1159/000109324
Publisher site
See Article on Publisher Site

Abstract

The effects of 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent selective inhibitor of hepatocyte endoplasmic reticulum Ca<sup>2+</sup>-ATPase, were functionally examined in rat aorta in order to assess whether tBuBHQ also acts as a Ca<sup>2+</sup> pump inhibitor of sarcoplasmic reticulum (SR) in vascular smooth muscle. tBuBHQ elicited a slowly developing and gradually decreasing contraction which was dependent on extracellular Ca<sup>2+</sup>. We utilize the phenylephrine (PE)-induced transient contractile response in Ca<sup>2+</sup>-free medium as an indirect index on the status of intracellular Ca<sup>2+</sup> store. When preparations, depleted of their PE-sensitive Ca<sup>2+</sup> store, were allowed to replete their stores in Ca<sup>2+</sup>-containing medium, a sustained contraction in tBuBHQ-treated preparations was observed, whereas in untreated control preparations, readministration of Ca<sup>2+</sup> elicited no contraction, or occasionally a weak, transient contraction. In control tissues subsequent application of PE in Ca<sup>2+</sup>-free medium after Ca<sup>2+</sup> 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 Ca<sup>2+</sup> 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<sup>2+</sup>-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 Ca<sup>2+</sup> pump inhibitor, interfering with effective refilling of PE-sensitive intracellular Ca<sup>2+</sup> stores.

Journal

Neurosignals – Karger

Published: Jan 1, 1992

Keywords: 2,5-Di-(tert-butyl)-1,4-benzohydroquinone; Aortic muscle, rat; Sarcoplasmic reticulum; Ca 2+ pump; Ca 2+ mobilization

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