Rho a/rho kinase: human umbilical artery mrna expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction
Friel, A. M Sexton, D. J O'Reilly, M. W Smith, T. J Morrison, J. J
Friel, A. M
Sexton, D. J
O'Reilly, M. W
Smith, T. J
Morrison, J. J
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Publication Date
2006-06-30
Type
Article
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Citation
Friel, A. M; Sexton, D. J; O'Reilly, M. W; Smith, T. J; Morrison, J. J (2006). Rho a/rho kinase: human umbilical artery mrna expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction. Reproduction 132 (1), 169-176
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 11) in the umbilical artery from normotensive and pre eclamptic women and (2) to determine whether the effects of two isoprostanes, 8-iso prostaglandin F-2 alpha (8-iso PGF2 alpha) and 8-iso, prostaglandin E-2 (8-iso PGE(2)), on umbilical artery tone, were mediated via the Rho kinase pathway. Real-time RT-PCR using primers for Rho A, ROCK I and ROCK 11 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 PGE(2), 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.
Funder
Publisher
BioScientifica
Publisher DOI
10.1530/rep.1.01088
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Attribution-NonCommercial-NoDerivs 3.0 Ireland