Involvement of K+ATP channels in nitric oxide-induced inhibition of spontaneous contractile activity of the nonpregnant human myometrium

Nitric oxide (NO), an important endogenous substance, is known to be a strong relaxant of smooth muscle, including myometrium. It has been postulated that the relaxing effect of NO on smooth muscle is achieved by the stimulation of soluble guanylyl cyclase, which leads to an increase in the cyclic guanosine 3',5'-monophosphate (cGMP) levels and hyperpolarization of the cellular membrane. The aim of our study was to investigate the involvement of K-ATP(+) channels in the mechanism of cGMP-independent nitric oxide-induced inhibition of contractile activity of the nonpregnant human myometrium, obtained at hysterectomy. Nitric oxide's influence on contractile activity was recorded in the presence of methylene blue and glybenclamide, blockers of soluble guanylyl cyclase and K-ATP(+) channels, respectively. Nitric oxide, generated by the NO donor DEA/NO, caused a dose-dependent inhibition of the spontaneous contractile activity of human nonpregnant myometrium. Preincubation with methylene blue (5 mu M) did not prevent NO-induced relaxation of uterine strips, while 1.5 mu M glybenclamide blocked this effect. Our results indicate that nitric oxide relaxes human non-pregnant uterus through K-ATP(+) channels, independent of the cGMP pathway. (C) 1998 Academic Press.