Colas B, Slama M, Collin T, Safar M, Andrejak M
Laboratoire de Pharmacologie et Physiopathologie Cardiovasculaire, Faculté de Médecine, Amiens, France.
Eur J Pharmacol. 2000 Nov 10;408(1):63-7. doi: 10.1016/s0014-2999(00)00704-4.
Methyclothiazide (MCTZ), a thiazide diuretic, inhibits the contractile response induced by norepinephrine in aortic rings from 12-week-old spontaneously hypertensive rats (SHR). Although not modified by indomethacin, this inhibition was attenuated by either mechanical removal of the endothelium or N omega-nitro-L-arginine (NOLA) treatment. These results suggest that the MCTZ effects on the norepinephrine-evoked vascular response are mediated by an endothelium-dependent mechanism involving endothelium-dependent relaxing factor (EDRF)/nitric oxide (NO) release. MCTZ was also found to alter the contractile response induced by the addition of Ca(2+) to a depolarizing solution, and this inhibitory effect was partially abolished by NOLA application. Our data led us to propose that MCTZ relaxes aortic rings, resulting in an endothelium-dependent relaxation phenomenon that could even be reinforced under high-K(+) depolarizing conditions.
甲氯噻嗪（MCTZ）是一种噻嗪类利尿剂，可抑制12周龄自发性高血压大鼠（SHR）主动脉环中去甲肾上腺素诱导的收缩反应。尽管吲哚美辛对此无影响，但这种抑制作用可通过机械去除内皮或Nω-硝基-L-精氨酸（NOLA）处理而减弱。这些结果表明，MCTZ对去甲肾上腺素诱发的血管反应的作用是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的。还发现MCTZ可改变向去极化溶液中添加Ca(2+)所诱导的收缩反应，并且NOLA的应用可部分消除这种抑制作用。我们的数据使我们提出，MCTZ可使主动脉环舒张，导致内皮依赖性舒张现象，在高钾去极化条件下甚至可能增强。
