Wu C C, Chen S J, Yen M H
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Life Sci. 1999;64(26):2471-8. doi: 10.1016/s0024-3205(99)00204-0.
Recent studies have shown that nitric oxide (NO) modulates K+-channel activity which play an important role in controlling vascular tone. The formation of cyclic guanosine 3',5'-monophosphate (cyclic GMP) has also been recognized to be associated with the vasodilatory effect of NO. Both cyclic GMP and NO increase whole-cell K+-current by activating Ca2+-activated K+-channels (K(Ca)-channels). Here, we show evidence that activators of soluble guanylyl cyclase sodium nitroprusside or 3-morpholino-sydnonimine (SIN-1), and an analogue of cyclic GMP 8-bromo-cyclic GMP enhance the relaxation induced by cromakalim which is blocked by glibenclamide (a specific inhibitor of ATP-sensitive K+-channels [K(ATP)-channels]), and partially attenuated by methylene blue (an inhibitor of cyclic GMP formation). However, this is not due to the increase of cyclic GMP level by cromakalim itself because the relaxation induced by cromakalim is not associated with the changes of cyclic GMP level formed in the aortic smooth muscle. Thus, it is most likely that cyclic GMP also modulates activity of K(ATP)-channels, in addition to K(Ca)-channels, in the rat aorta.
最近的研究表明,一氧化氮(NO)可调节钾通道活性,而钾通道在控制血管张力方面发挥着重要作用。环磷酸鸟苷(cGMP)的形成也被认为与NO的血管舒张作用有关。cGMP和NO均通过激活钙激活钾通道(K(Ca)通道)来增加全细胞钾电流。在此,我们提供证据表明,可溶性鸟苷酸环化酶激活剂硝普钠或3-吗啉代西多胺(SIN-1)以及cGMP类似物8-溴-cGMP可增强由克罗卡林诱导的舒张作用,该作用被格列本脲(一种ATP敏感性钾通道[K(ATP)通道]的特异性抑制剂)阻断,并被亚甲蓝(一种cGMP形成抑制剂)部分减弱。然而,这并非由于克罗卡林本身导致cGMP水平升高,因为克罗卡林诱导的舒张作用与主动脉平滑肌中形成的cGMP水平变化无关。因此,很可能cGMP除了调节K(Ca)通道外,还调节大鼠主动脉中K(ATP)通道的活性。