Roles of potassium channels and nitric oxide in modulation of uterine contractions in rat pregnancy

OBJECTIVE: We sought to study the involvement of potassium channels in the inhibition by nitric oxide of spontaneous contractions in isolated uterine rings from midterm and term pregnant rats. STUDY DESIGN: Uterine rings from Sprague-Dawley rats at midterm and term ge station were used for isometric tension recording. The inhibition of sponta neous contractile activity by potassium channel openers and nitric oxide wa s studied in the absence and presence of potassium channel inhibitors. RESULTS: The adenosine triphosphate-dependent potassium channel opener levc romakalim inhibited spontaneous contractions in rings from both midterm and term pregnant rats in a concentration-dependent manner, and the effects we re significantly attenuated by pretreatment with selective inhibitor of the adenosine triphosphate-dependent potassium channel inhibitor glibenclamide . The opener of calcium-dependent potassium channel NS 1619 inhibited spont aneous contractions in rings from midterm but significantly less so in ring s from term pregnant rats in a concentration-dependent manner, and the effe ct was significantly attenuated by pretreatment with potassium channel inhi bitors tetraethylammonium and tetrabutylammonium but not with glibenclamide . Rings from midterm and term pregnant rats were more sensitive to the inhi bitory effect of levcromakalim compared with NS 1619. Nitric oxide donor di ethylamine-nitric oxide inhibited spontaneous contractions in rings from mi dterm but significantly less in rings from term pregnant rats in a concentr ation-dependent manner, and the effect was attenuated by tetraethylammonium and tetrabutylammonium but not by glibenclamide. CONCLUSIONS: There is gestational age-dependent refractoriness to calcium-d ependent potassium but not adenosine triphosphate-dependent potassium chann el opener-induced inhibition of spontaneous contractile activity of isolate d rat uterine rings. Nitric oxide inhibits uterine contractions by opening of calcium-dependent potassium channels in pregnant rat myometrium. Refract oriness to nitric oxide toward term may result from decreased probability t o open or number of calcium-dependent potassium channels.