Differential effects of insulin-sensitizers troglitazone and rosiglitazone on ion currents in rat vascular myocytes
Differential effects of insulin-sensitizers troglitazone and rosiglitazone on ion currents in rat vascular myocytes
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DOI：
10.1016/s0014-2999(99)00020-5
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发表时间：
1999-02-26
影响因子：
5
通讯作者：
Aaronson, PI
中科院分区：
文献类型：
--
作者：
Knock, GA;Mishra, SK;Aaronson, PI
胰岛素增敏噻唑烷二酮类药物如曲格列酮和吡格列酮已被证明在体内可降低血压，在体外可引起血管舒张。罗格列酮（BRL 49653）是一种新型噻唑烷二酮，据报道不会引起血管舒张。因此，我们比较了曲格列酮和rosglitazone对大鼠主动脉和肺动脉平滑肌细胞Ca 2+和K+电流的影响。采用传统的全细胞膜片钳技术记录电流。这两种药物降低了大鼠主动脉细胞的电压门控（L型）钙电流，曲格列酮和罗格列酮在2和10 μ M时分别具有半数最大电流抑制作用。Troglitazone，2 μ M和罗格列酮，20 μ M引起类似的超极化位移12 mV的电位依赖性的Ca 2+电流的可用性。曲格列酮（20 μ M）产生了显着的块的四乙基铵和paxilline敏感的Ca 2+激活的K+电流，而罗格列酮（20 μ M和60 μ M）略有增强这一电流。大鼠肺动脉平滑肌细胞存在明显的延迟整流钾电流。曲格列酮可有效阻断该电流（< 1 μ M时的半数最大抑制），而罗格列酮在10和60 μ M时引起较小的抑制。这些结果表明，曲格列酮对血管平滑肌细胞中多种离子电流具有相对有效的阻断作用。罗格列酮对Ca ~（2+）电流和延迟整流K ~+电流的作用较弱，但作用相似，但可增强Ca ~（2+）激活的K ~+电流。(C)1999 Elsevier Science B. V.保留所有权利。
Insulin-sensitizing thiazolidinediones such as troglitazone and pioglitazone have been shown to lower blood pressure in vivo and cause vasorelaxation in vitro. Rosiglitazone (BRL 49653) is a novel thiazolidinedione which has been reported not to cause vasoleraxation. We therefore compared the effects of troglitazone and rosglitazone on Ca2+ and K+ currents in rat aorta and pulmonary artery smooth muscle cells. Currents were recorded with the conventional whole cell patch clamp technique. Both drugs reduced the voltage-gated (L-type) Ca2+ current in rat aorta cells, with half-maximal current inhibition by troglitazone and rosiglitazone at 2 and 10 mu M: respectively. Troglitazone, 2 mu M and rosiglitazone, 20 mu M caused a similar hyperpolarizing shift of 12 mV in the potential-dependence of Ca2+ current availability. Troglitazone (20 mu M) produced a marked block of the tetraethylammonium- and paxilline-sensitive Ca2+ activated K+ current, while rosiglitazone (20 mu M and 60 mu M) slightly enhanced this current. Rat pulmonary artery smooth muscle cells have a prominent delayed rectifier K+ current. Troglitazone produced a potent block of this current (half-maximal inhibition at < 1 mu M), while rosiglitazone caused a smaller inhibition at 10 and 60 mu M. These results show that troglitazone has relatively potent blocking effects on a wide variety of ion currents in vascular smooth muscle cells. Rosiglitazone exerts less potent, but similar effects on the Ca2+ current and delayed rectifier K+ current, but it enhances the Ca2+-activated K+ current. (C) 1999 Elsevier Science B.V. All rights reserved.