Effects of L-type Ca2+-channel blockade, K+ATP-channel opening and nitric oxide on human uterine contractility in relation to gestational age and labour

Abstract

Relative uterine inactivity during pregnancy changes to vigorous rhythmic contractility during labour. We hypothesized that mechanisms involved in the regulation of uterine quiescence and contractility differ between term and preterm myometrium and in labour and non-labour states. Myometrial strips, prepared from biopsies taken at Caesarean section from labouring and non-labouring women preterm and at term, were mounted in organ chambers for isometric tension recording. Oxytocin (10(-9) mol/l) was added to maintain stable contractions, and effects of various inhibitors of uterine contractility were studied. The inhibitory effects of L-type Ca(2+)-channel blocker nifedipine and ATP-sensitive K(+)-channel opener pinacidil were greater in myometrium from the non-labour versus the labour group, both preterm and at term. In addition, pinacidil's effect was greater at term compared with preterm in the non-labour group. Mg(2+) and the nitric oxide donor sodium nitroprusside significantly inhibited contractility in all groups without significant differences with regard to labour or gestational age. Decreased inhibition of human uterine contractility by L-type Ca(2+)-channel blockers and K(+)(ATP)-channel openers in preterm and term labour may reflect changes in expression and activity of these channels. Effects of nitric oxide and Mg(2+) are not affected by gestational age or labour.

Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics

“…Nifedipine (5 nM) inhibited the amplitude of oxytocin-stimulated contractions with less effect on frequency [41] and at μM concentrations completely eliminated contractile activity [42]. The effect of nifedipine on human myometrial strips was more marked in term not-in-labor than in term-labor specimens [43]. A significant proportion of oxytocin and PGF2α-induced contractions and increases in [Ca 2+ ] i in late pregnant guinea pig myometrium was attributed to Ca 2+ entry inhibited by L-type Ca blockers [44], as was the response in pregnant rat myometrial cell [45].…”

Potassium channels and uterine function

“…These findings may indicate that in humans, down-regulation of K ATP channels may contribute to increased uterine excitability and induction of labor contractions in term pregnancy. In human myometrium, the expression of K ATP depends on both the gestational stage and the presence of labor contractions [41]. Pinacidil, a K ATP opener, inhibits oxytocin-induced contractions in late pregnant non-laboring myometrium [41].…”

“…In human myometrium, the expression of K ATP depends on both the gestational stage and the presence of labor contractions [41]. Pinacidil, a K ATP opener, inhibits oxytocin-induced contractions in late pregnant non-laboring myometrium [41]. This effect was attenuated in laboring myometrium from term and preterm uteri.…”

“…Between the two latter groups, inhibition was more pronounced in term labor uterine strips. The differential effects of pinacidil may reflect altered activity and/or expression levels of K ATP channels in gestation and labor [41].…”

In Vitro Contractile Response of Rabbit Myometrium to BKCa and KATP Potassium Channel Openers

“…Mandi et al (2005) showed the ability of pinacidil to inhibit spontaneous rhythmic contractions and to antagonize oxytocin-induced contraction in the pregnant goat myometrium collected at the mid-gestation. The study of Longo et al (2003) also demonstrated that the increase in the expression and function of ATP-sensitive potassium channels may play an important role in the uterine preparation for pre-term or term labour.…”