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

Toshiaki Okawa, Yuri P. Vedernikov, George Saade, Monica Longo, Gayle Olson, Kristof Chwalisz, Robert E. Garfield

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalAmerican Journal of Obstetrics and Gynecology
Volume181
Issue number3
DOIs
StatePublished - 1999

Fingerprint

Uterine Contraction
Potassium Channels
Nitric Oxide
Pregnancy
Calcium-Activated Potassium Channels
Glyburide
Cromakalim
Tetraethylammonium
Adenosine Triphosphate
Nitric Oxide Donors
Myometrium
potassium oxide
Gestational Age
Sprague Dawley Rats
Potassium
Calcium

Keywords

  • Adenosine triphosphate-dependent potassium channels
  • Calcium-dependent potassium channels
  • Myometrium
  • Nitric oxide
  • Pregnancy

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Roles of potassium channels and nitric oxide in modulation of uterine contractions in rat pregnancy. / Okawa, Toshiaki; Vedernikov, Yuri P.; Saade, George; Longo, Monica; Olson, Gayle; Chwalisz, Kristof; Garfield, Robert E.

In: American Journal of Obstetrics and Gynecology, Vol. 181, No. 3, 1999, p. 649-655.

Research output: Contribution to journalArticle

Okawa, Toshiaki ; Vedernikov, Yuri P. ; Saade, George ; Longo, Monica ; Olson, Gayle ; Chwalisz, Kristof ; Garfield, Robert E. / Roles of potassium channels and nitric oxide in modulation of uterine contractions in rat pregnancy. In: American Journal of Obstetrics and Gynecology. 1999 ; Vol. 181, No. 3. pp. 649-655.
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abstract = "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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T1 - Roles of potassium channels and nitric oxide in modulation of uterine contractions in rat pregnancy

AU - Okawa, Toshiaki

AU - Vedernikov, Yuri P.

AU - Saade, George

AU - Longo, Monica

AU - Olson, Gayle

AU - Chwalisz, Kristof

AU - Garfield, Robert E.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - Adenosine triphosphate-dependent potassium channels

KW - Calcium-dependent potassium channels

KW - Myometrium

KW - Nitric oxide

KW - Pregnancy

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