Molecular Human Reproduction, Vol. 8, No. 2, 196-200,
February 2002
© 2002 European Society of Human Reproduction and Embryology
Implantation and pregnancy |
Expression and modulation of Rho kinase in human pregnant myometrium
1 Department of Obstetrics and Gynaecology, National University of Ireland Galway, Clinical Science Institute, University College Hospital, Newcastle Road, Galway and 2 National Diagnostics Centre, BioResearch Ireland, National University of Ireland Galway, University Road, Galway, Ireland
There is little information outlining the role of Rho kinase, RhoA, and calcium sensitization in regulation of human uterine contractility during pregnancy. The aims of this study were to investigate the expression of RhoA, and the Rho kinases ROCK I and ROCK II in human pregnant myometrium, to evaluate the effects of Rho kinase inhibition on pregnant human myometrial contractility in vitro, and to compare these effects with those of the calcium channel blocker nifedipine. RTPCR using primers for RhoA, ROCK I and ROCK II was performed on mRNA isolated from human pregnant myometrium. Isometric recording was performed in isolated myometrial strips obtained at Caesarean section. The effects of the Rho kinase inhibitor Y-27632 (1 nmol/l to 10 mmol/l), and nifedipine (1 nmol/l to 10 mmol/l), on oxytocin (0.5 nmol/l) induced contractions were measured and compared. Expression of RhoA, ROCK I and ROCK II mRNA was identified in human pregnant myometrium (n = 3). Y-27632 exerted a potent relaxant effect on myometrial contractility with a pD2 value (± SEM) of 7.63 ± 0.38 (n = 6). The maximum net relaxant effect (± SEM) was 72.3 ± 6.1% (n = 6). Corresponding values for nifedipine were 7.24 ± 0.48 (n = 6; P = 0.469) and 93.40 ± 3.1% (n = 6; P = 0.028). Rho A/Rho kinase-mediated calcium sensitization may play role in the physiology of human parturition, and pharmacological inhibition of this pathway may therefore provide a novel approach to tocolysis for pre-term labour.
human myometrium/preterm labour/Rho kinase/tocolysis
3 To whom correspondence should be addressed. E-mail: john.morrison{at}nuigalway.ie
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