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Title
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Basal activity of voltage-gated channels controls the -mediated contraction by -adrenoceptor stimulation of mouse aorta segments
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Author
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Abstract
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| α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca2+ release from sarcoplasmic reticulum Ca2+ stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca2+ release from the contractile and IP3-sensitive Ca2+ store is under the continuous dynamic control of time-independent basal Ca2+ influx via L-type voltage-gated Ca2+ channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca2+ (0Ca) to measure phasic isometric contractions. They gradually decreased with time in 0Ca, were inhibited with 2-aminoethoxydiphenyl borate, and declined with previous membrane potential hyperpolarization (levcromakalim) or with previous inhibition of LCC (diltiazem). Former basal stimulation of LCC with depolarization (15 mM K+) or with BAY K8644 increased the subsequent phasic contractions by phenylephrine in 0Ca. Although exogenous NO (diethylamine NONOate) reduced the phasic contractions by phenylephrine, stimulation of endothelial cells with acetylcholine in 0Ca failed to attenuate these phasic contractions. Finally, inhibition of the basal release of NO with NΩ-nitro-L-arginine methyl ester also attenuated the phasic contractions by phenylephrine. Results indicated that α1-adrenoceptor stimulation with phenylephrine causes phasic contractions, which are controlled by basal LCC and endothelial NO synthase activity. Endothelial NO release by acetylcholine was absent in 0Ca. Given the growing interest in the active regulation of arterial compliance, the dependence of contractile SR Ca2+ store-refilling in basal conditions on the activity of LCC and basal eNOS may contribute to a more thorough understanding of physiological mechanisms leading to arterial stiffness. |
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Language
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English
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Source (journal)
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European journal of pharmacology. - Amsterdam, 1967, currens
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Publication
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Amsterdam
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North-Holland
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2015
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ISSN
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0014-2999
[print]
1879-0712
[online]
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DOI
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10.1016/J.EJPHAR.2015.04.011
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Volume/pages
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760
(2015)
, p. 163-171
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ISI
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000355664200020
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Pubmed ID
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25913240
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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