Colas B, Colas J L, Masson H, Slama M, Collin T, Andrejak M
Arch Mal Coeur Vaiss. 2000 Aug;93(8):901-4.
The possible involvement of calcium and potassium channels in mediating the vascular actions of methyclothiazide (MCTZ), a thiazide diuretic, was investigated in isolated aortic rings from 12 week-old hypertensive rats. MCTZ (10(-4) M) inhibits the contractile response induced by addition of Ca2+ to a depolarizing solution, the maximal contracture is reduced by 87.16 +/- 6.4%. Furthermore this inhibitory effect was unaffected by charybdotoxine a selective blocker of calcium-activated K+ channels (Kca). This suggesting that MCTZ inhibits voltage-gated Ca2+ channels and blunts the Ca2+ entry into vascular smooth muscle cells. This inhibition was partially attenuated by either mechanical removal of the endothelium or N omega-nitro-L-arginine (NOLA) treatment, suggesting that MCTZ effects are also mediated by an endothelium-dependent mechanism involving endothelium-dependent relaxing factor (EDRF)/nitric oxide (NO) release. Taken together, these observations could point to a role of voltage-gated Ca2+ channels and endothelial release of EDRF/NO in the antihypertensive action of MCTZ.
在12周龄高血压大鼠的离体主动脉环中，研究了钙通道和钾通道在介导噻嗪类利尿剂甲氯噻嗪（MCTZ）血管作用中的可能参与情况。MCTZ（10⁻⁴ M）抑制了向去极化溶液中添加Ca²⁺所诱导的收缩反应，最大挛缩减少了87.16±6.4%。此外，这种抑制作用不受钙激活钾通道（Kca）的选择性阻滞剂蝎毒素的影响。这表明MCTZ抑制电压门控Ca²⁺通道，并减弱Ca²⁺进入血管平滑肌细胞。通过机械去除内皮或N⁻硝基-L-精氨酸（NOLA）处理，这种抑制作用部分减弱，表明MCTZ的作用也由涉及内皮依赖性舒张因子（EDRF）/一氧化氮（NO）释放的内皮依赖性机制介导。综上所述，这些观察结果可能表明电压门控Ca²⁺通道和内皮释放EDRF/NO在MCTZ的降压作用中发挥作用。
