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

Sep 16, 1999American journal of obstetrics and gynecology

How potassium channels and nitric oxide influence uterine contractions during rat pregnancy

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Abstract

The potassium channel opener levcromakalim inhibited spontaneous contractions in isolated uterine rings from pregnant rats in a concentration-dependent manner.

Inhibition of contractions was significantly reduced when the adenosine triphosphate-dependent potassium channel inhibitor glibenclamide was administered.
The calcium-dependent potassium channel opener NS 1619 inhibited contractions in midterm pregnant rats but had a significantly lesser effect in term pregnant rats.
Sensitivity to levcromakalim was higher in both midterm and term pregnant rats compared to NS 1619.
Nitric oxide inhibited spontaneous contractions in midterm pregnant rats more effectively than in term pregnant rats.
The inhibitory effects of nitric oxide were diminished by potassium channel inhibitors tetraethylammonium and tetrabutylammonium, but not by glibenclamide.
Refractoriness to nitric oxide at term may be due to a reduced likelihood of calcium-dependent potassium channels opening.

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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 gestation were used for isometric tension recording. The inhibition of spontaneous contractile activity by potassium channel openers and nitric oxide was studied in the absence and presence of potassium channel inhibitors.

RESULTS: The adenosine triphosphate-dependent potassium channel opener levcromakalim inhibited spontaneous contractions in rings from both midterm and term pregnant rats in a concentration-dependent manner, and the effects were 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 spontaneous contractions in rings from midterm but significantly less so in rings from term pregnant rats in a concentration-dependent manner, and the effect was significantly attenuated by pretreatment with potassium channel inhibitors tetraethylammonium and tetrabutylammonium but not with glibenclamide. Rings from midterm and term pregnant rats were more sensitive to the inhibitory effect of levcromakalim compared with NS 1619. Nitric oxide donor diethylamine-nitric oxide inhibited spontaneous contractions in rings from midterm but significantly less in rings from term pregnant rats in a concentration-dependent manner, and the effect was attenuated by tetraethylammonium and tetrabutylammonium but not by glibenclamide.

CONCLUSIONS: There is gestational age-dependent refractoriness to calcium-dependent potassium but not adenosine triphosphate-dependent potassium channel opener-induced inhibition of spontaneous contractile activity of isolated rat uterine rings. Nitric oxide inhibits uterine contractions by opening of calcium-dependent potassium channels in pregnant rat myometrium. Refractoriness to nitric oxide toward term may result from decreased probability to open or number of calcium-dependent potassium channels.

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

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