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Expression Levels of mRNA for Rho A/Rho Kinase and Its Role in Isoprostane-Induced Vasoconstriction of Human Placental and Maternal Vessels

Department of Obstetrics and Gynaecology, National University of Ireland, Galway, Clinical Science Institute, University College Hospital, Galway, Ireland, National Centre for Biomedical Engineering Science National University of Ireland, Galway

Paul G. Hynes, BSc

Department of Obstetrics and Gynaecology, National University of Ireland, Galway, Clinical Science Institute, University College Hospital, Galway, Ireland, National Centre for Biomedical Engineering Science National University of Ireland, Galway

Donal J. Sexton, MB

Department of Obstetrics and Gynaecology, National University of Ireland, Galway, Clinical Science Institute, University College Hospital, Galway, Ireland

Terry J. Smith, PhD

National Centre for Biomedical Engineering Science National University of Ireland, Galway

John J. Morrison, MD

Department of Obstetrics and Gynaecology, National University of Ireland, Galway, Clinical Science Institute, University College Hospital, Galway, Ireland, john.morrison{at}nuigalway.ie, National Centre for Biomedical Engineering Science National University of Ireland, Galway

Preeclampsia is characterized by intense and prolonged vasoconstriction. Rho A—mediated calcium sensitization is central to prolonged contractility of vascular smooth muscle. The aims of this study are (1) to investigate mRNA expression levels of Rho A/Rho kinases in placental tissues from normotensive and preeclamptic women and (2) to investigate the effects of 2 isoprostanes, 8-iso prostaglandin F₂ (8-iso PGF₂ ) and 8-iso prostaglandin E₂ (8-iso PGE₂), on small placental and myometrial vessel resistance and to determine if their effects were mediated via the Rho kinase pathway. Real-time reverse transcription polymerase chain reaction for Rho A, ROCK I, and ROCK II was performed on total RNA from normotensive and preeclamptic placentae. The effects of 8- iso PGF₂ and 8-iso PGE₂ (alone and with the specific Rho kinase inhibitor Y-27632) on placental and myometrial vessels (<400 µm) were measured and compared with control recordings. Rho A mRNA expression levels were significantly higher in placentae from preeclamptic women than in placentae from normotensive women (P < .01). There was no significant difference in expression levels of ROCK I and ROCK II between both tissue types (P > .05). Both isoprostanes exerted a significant concentration-dependent vasocontractile effect on both vessel types (P < .001). This effect was antagonized by Y-27632 in placental arteries but not in myometrial arteries. Increased Rho A mRNA expression in placentae from preeclamptic women is suggestive of a role for the Rho kinase pathway in the modulation of the placental vasculature in this condition. Isoprostanes exert their vasocontractile effect, in placental vasculature, in part via the Rho kinase pathway.

Key Words: Preeclampsia • pregnancy • placenta • Rho A.

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