Cyclic GMP regulates cromakalim-induced relaxation in the rat aortic smooth muscle: Role of cyclic GMP in K-ATP-channels

Recent studies have shown that nitric oxide (NO) modulates K+-channel activ ity which play an important role in controlling vascular tone. The formatio n of cyclic guanosine 3',5'-monophosphate (cyclic GMP) has also been recogn ized to be associated with the vasodilatory effect of NO. Both cyclic GMP a nd NO increase whole-cell K+-current by activating Ca2+-activated K+-channe ls (K-Ca-channels). Here, we show evidence that activators of soluble guany lyl cyclase sodium nitroprusside or 3-morpholino-sydnonimine (SIN-1), and a n analogue of cyclic GMP 8-bromo-cyclic GMP enhance the relaxation induced by cromakalim which is blocked by glibenclamide (a specific inhibitor of AT P-sensitive K+-channels [K-ATP-channels]), and partially attenuated by meth ylene blue (an inhibitor of cyclic CMP formation). However, this is not due to the increase of cyclic GMP level by cromakalim itself because the relax ation induced by cromakalim is not associated with the changes of cyclic GM P level formed in the aortic smooth muscle. Thus, it is most likely that cy clic GMP also modulates activity of K-ATP-channels, in addition to K-Ca-cha nnels, in the rat aorta.