Delivery of the fetus and placenta at term requires precise regulation of the mechanisms underlying uterine contractility. Recent evidence indicates that agonist-induced Ca²⁺-sensitisation of smooth contractility, including the uterus, involves activation of a rho-associated kinase (ROK) signalling cascade (Lee et al. 2001). In addition, thromboxane receptor stimulation increased ROK activity in cultured human myometrial cells (Moore et al. 2002). Therefore, we have analysed the effects of pharmacological inhibition of ROK on in vitro thromboxane-stimulated uterine contractility. This was also compared with the effect of ROK inhibition on oxytocin-stimulated contractions of myometria isolated from (a) near-term (gestation day 19-21) pregnant rats (killed by cervical dislocation following stunning in accordance with national guidelines;) or (b) non-labouring term humans (following written informed consent according to local ethics committee guidelines; gestation 37-41 weeks). Small myometrial strips were dissected and mounted for contractile activation on standard organ baths in HCO₃^–-buffered physiological saline solution (37 °C, 95 % air and 5 % CO₂). Addition of the ROK inhibitor HA1077 (10 µM) significantly reduced the amplitude and duration of contractions to 10 µM of the thromboxane mimetic U46619 (P < 0.05, Wilcoxon non-parametric test); peak contractile amplitude was reduced by 26 ± 6.0 % of control (mean ± S.E.M., n = 8). For oxytocin-stimulated contractions (0.1 µM), addition of another ROK inhibitor, Y-27632 (10 µM), also significantly reduced contractile duration and amplitude; peak contractile amplitude in myometria of humans was reduced by 31 ± 3.7 % (n = 8) similar to the findings of others (Kupittayanant et al. 2001) and decreased by 44 ± 7.1 % (n = 6) in rat myometria. Western blotting analysis of homogenised tissue indicated strong expression of ROKα isoform in myometria from both term rats and humans. The data indicate that pharmacological inhibitors of ROK partly reduce in vitro agonist-induced contractile force of intact myometria of pregnant rats and humans. Further investigation is required to determine the importance of ROK activation in (i) uterine contractions during labour at term and (ii) the manifestation of preterm labour that may be linked to enhanced thromboxane receptor stimulation.

This work was supported by Tommy’s, the Baby Charity and the Royal Society.