Leloup Arthur J, Van Hove Cor E, De Meyer Guido R Y, Schrijvers Dorien M, Fransen Paul
Laboratory of Physiopharmacology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Laboratory of Pharmacology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Eur J Pharmacol. 2015 Aug 5;760:163-71. doi: 10.1016/j.ejphar.2015.04.011. Epub 2015 Apr 22.
α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous dynamic control of time-independent basal Ca(2+) influx via L-type voltage-gated Ca(2+) channels (LCC) residing in their window voltage range. Mouse aortic segments were α1-adrenoceptor stimulated with phenylephrine in the absence of external Ca(2+) (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 N(Ω)-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 Ca(2+) 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.
α1-肾上腺素能受体对小鼠主动脉的刺激通过刺激肌醇三磷酸（IP3）受体，使细胞内钙离子从肌浆网钙库释放。据推测，这种从收缩性且对IP3敏感的钙库释放钙离子的过程，受到通过位于其窗口电压范围内的L型电压门控钙通道（LCC）进行的与时间无关的基础钙内流的持续动态控制。在无细胞外钙（0Ca）的情况下，用去氧肾上腺素刺激小鼠主动脉段的α1-肾上腺素能受体，以测量等长相收缩。在0Ca条件下，它们随时间逐渐降低，被2-氨基乙氧基二苯硼酸盐抑制，并随着先前的膜电位超极化（左旋克罗卡林）或先前对LCC的抑制（地尔硫䓬）而下降。先前用去极化（15 mM K(+)）或BAY K8644对LCC进行基础刺激，可增加随后在0Ca条件下去氧肾上腺素引起的相收缩。尽管外源性一氧化氮（二乙胺NONOate）可降低去氧肾上腺素引起的相收缩，但在0Ca条件下用乙酰胆碱刺激内皮细胞未能减弱这些相收缩。最后，用N(Ω)-硝基-L-精氨酸甲酯抑制基础一氧化氮释放也减弱了去氧肾上腺素引起的相收缩。结果表明，用去氧肾上腺素刺激α1-肾上腺素能受体可引起相收缩，其受基础LCC和内皮型一氧化氮合酶活性的控制。在0Ca条件下，乙酰胆碱不会释放内皮一氧化氮。鉴于对动脉顺应性主动调节的兴趣日益增加，基础条件下收缩性肌浆网钙库再充盈对LCC活性和基础内皮型一氧化氮合酶的依赖性，可能有助于更全面地理解导致动脉僵硬的生理机制。
