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.


METHODS
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.
Okawa
T
T
Department of Obstetrics, University of Texas Medical Branch, Galveston, USA.
Vedernikov
Y P
YP
Saade
G R
GR
Longo
M
M
Olson
G L
GL
Chwalisz
K
K
Garfield
R E
RE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007743:Labor, Obstetric / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011247:Pregnancy; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D001562:Benzimidazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D019806:Cromakalim; C086491:NS 1619; D009569:Nitric Oxide; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; C009405:tetrabutylammonium; D005905:Glyburide