Rho A/Rho kinase: Human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Anne Friel, Donal J. Sexton, Michael W. O'Reilly, Terry J. Smith, John J. Morrison

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Pre eclampsia represents a state of increased or prolonged vasoconstriction, partially linked to the potent vasocontractile effect of isoprostanes. The process of Rho A-mediated calcium sensitisation is inherent to a state of prolonged contractility in many smooth muscle types. The aim of this study was (1) to investigate mRNA expression levels of Rho A and Rho kinase isoforms (I and II) in the umbilical artery from normotensive and pre eclamptic women and (2) to determine whether the effects of two isoprostanes, 8-iso prostaglandin F (8-iso PGF2α) and 8-iso prostaglandin E2 (8-iso PGE2), on umbilical artery tone, were mediated via the Rho kinase pathway. Real-time RT-PCR using primers for Rho A. ROCK I and ROCK II was performed on total RNA isolated from umbilical artery specimens obtained from normotensive and pre eclamptic women. The effects of both isoprostanes (n=6) (in the absence and presence of the specific Rho kinase inhibitor Y-27632), on umbilical artery tone were measured, and compared with control recordings. Rho A mRNA expression levels were significantly lower in umbilical artery samples obtained from pre eclamptic women (n=4) in comparison to those from normotensive women (n=6) (P<0.05). ROCK I and ROCK II mRNA levels were similar in both vessel types (P>0.05). Both isoprostanes exerted a significant concentration-dependent vasocontractile effect (n=7) (P<0.001) on umbilical artery. For 8-iso PGE2, this effect was antagonised by Y-27632 (n=6) (P<0.01). The significant reduction of Rho A mRNA levels in umbilical arteries from pregnancies complicated by pre eclampsia may serve to counteract the diminished perfusion associated with the pathophysiology of pre eclampsia. The vasocontractile effect of 8-iso PGE2 in pre eclampsia may in part be mediated via the Rho kinase pathway.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalReproduction
Volume132
Issue number1
DOIs
Publication statusPublished - Jul 2006

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