Effect of nitric oxide on contractions of uterine and cervical tissues from pregnant rats.
Our objective was to evaluate the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in rat uterine and cervical contractility at mid- and late gestation. Rings of uterus and cervix from Sprague Dawley rats on day 14 of pregnancy (mid-) and day 21 of pregnancy (late) were equilibrated at 2 g passive tension in organ chambers filled with Krebs-Henseleit solution and bubbled with 5% CO2 in air (37 degrees C, pH approximately 7.4). Rings were treated with an inhibitor of outward potassium current, tetraethylammonium, to activate phasic contractions, and the concentration-response relationships to diethylamine/NO and 8-bromo-cGMP (8-br-cGMP) were assessed. Baseline spontaneous activity was significantly higher at term gestation in both uterine and cervical rings compared with mid-gestation. Spontaneous contractile activity was not apparent in cervical rings from rats in mid-gestation, but was persistent after treatment with tetraethylammonium. Oxyhemoglobin did not affect NO-induced inhibition of activation by tetraethylammonium contractile activity in either cervical or uterine tissues in mid- or late gestation. The 8-br-cGMP concentration-dependently inhibited tetraethylammonium-activated contractions that were more pronounced in uterine tissues compared with cervical tissues in both mid- and late gestation. We concluded that activation of the NO-cGMP pathway inhibits both uterine and cervical smooth muscle contractility. Both tissues demonstrated refractoriness to NO at term.
Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Texas Medical Branch, Galveston, TX, USA.
T
T
Okawa
Y P
YP
Vedernikov
G R
GR
Saade
R E
RE
Garfield
D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D009569:Nitric Oxide / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*
D004048:Diethylamines; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP