Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction.
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(2alpha) (8-iso PGF2alpha) 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 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 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 PGE(2) in pre eclampsia may in part be mediated via the Rho kinase pathway.
Friel
Anne M
AM
Department of Obstetrics and Gynaecology, National University of Ireland, Galway, Clinical Science Institute, University College Hospital, Newcastle Road, Galway, Ireland.
Sexton
Donal J
DJ
O'reilly
Michael W
MW
Smith
Terry J
TJ
Morrison
John J
JJ
D000209:Acute-Phase Proteins / Q000235:genetics*; D000577:Amides / Q000494:pharmacology; D000704:Analysis of Variance; D016022:Case-Control Studies; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D028421:Isoprostanes / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046509:Tissue Culture Techniques; D014469:Umbilical Arteries; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
D000209:Acute-Phase Proteins; D000577:Amides; D047908:Intracellular Signaling Peptides and Proteins; D028421:Isoprostanes; D020033:Protein Isoforms; D011725:Pyridines; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; C010781:acute-phase protein rho; C108830:Y 27632; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D015232:Dinoprostone; C011987:8-isoprostaglandin E2