Effects of pioglitazone on calcium channels in vascular smooth muscle.

Effects of pioglitazone on calcium channels in vascular smooth muscle.
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吡格列酮对血管平滑肌钙通道的影响。

DOI:
10.1161/01.hyp.24.2.170
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发表时间:
1994
期刊:
Hypertension (Dallas, Tex. : 1979)
影响因子:
--
通讯作者:
Peuler,JD
Peuler,JD
中科院分区:
--
文献类型:
--
作者:
Zhang,F;Sowers,JR;Ram,JL;Standley,PR;Peuler,JD

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吡格列酮是一种胰岛素增敏抗糖尿病药,对胰岛素抵抗性高血压大鼠具有降血压作用,并能减弱​​生长因子诱导的大鼠主动脉血管平滑肌细胞内 Ca2+ 的增加。为了确定电压依赖性 Ca2+ 通道的调节是否在这种关联中发挥作用,我们研究了吡格列酮对培养的大鼠主动脉 (a7r5) 和新鲜分离的大鼠尾动脉血管平滑肌细胞中电压依赖性电流的影响。两种细胞类型均采用全细胞膜片钳技术进行研究。在 Ba2+ 替代 Ca2+ 存在的情况下,通过电压斜坡引出通过 L 型 Ca2+ 通道的电流。使用双脉冲协议研究了 T 型 Ca2+ 电流,该协议能够隔离瞬态电流。在 a7r5 血管平滑肌细胞中,应用吡格列酮(5 和 10 μmol/L)2 分钟分别使 L 型电流降低 7.9 +/- 1.0% (n = 8)(平均值 +/- SEM,细胞数)和 14.5 +/- 3.0% (n = 9)(P < .01,双尾配对 t 检验)。相比之下,应用吡格列酮2分钟对T型Ca2+电流没有显着影响。在新鲜分离的尾动脉血管平滑肌细胞中,应用10μmol/L吡格列酮2分钟效果不显着(降低4.8+/-5.6%);然而,25 μmol/L 吡格列酮使 L 型电流降低 27.3 +/- 7.2% (n = 5) (P < .01)。单独应用 0.1% 或 0.2% 二甲亚砜(媒介物)两分钟对任一类型血管平滑肌细胞的电流均没有显着影响。(摘要截断为 250 字)
Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca2+ in rat aortic vascular smooth muscle cells. To determine whether modulation of voltage-dependent Ca2+ channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca2+ channels was elicited with a voltage ramp in the presence of Ba2+ substituted for Ca2+. T-type Ca2+ current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 mumol/L) reduced L-type current by 7.9 +/- 1.0% (n = 8) (mean +/- SEM, number of cells) and 14.5 +/- 3.0% (n = 9) (P < .01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca2+ current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 mumol/L pioglitazone had an insignificant effect (4.8 +/- 5.6% reduction); however, 25 mumol/L pioglitazone reduced L-type current by 27.3 +/- 7.2% (n = 5) (P < .01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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影响因子: --
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高血压中的血管肌肉钙通道调节
DOI: 10.1097/00005344-198900146-00011
发表时间: 1989
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影响因子: --
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DOI: 10.1172/jci113801
发表时间: 1988-12-01
影响因子: 15.9
作者:
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