8-isoprostaglandin-e2 and Pre-Eclampsia

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 F(2)( alpha) (8-iso PGF(2 alpha) ) and 8-iso prostaglandin E(2) (8-iso PGE(2)), 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 PGF(2 alpha) and 8-iso PGE(2) (alone and with the specific Rho kinase inhibitor Y-27632) on placental and myometrial vessels (<400 microm) 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.

Topics: Dinoprost; Dinoprostone; Female; Humans; Isoprostanes; Myometrium; Placenta; Pre-Eclampsia; Pregnancy; rho-Associated Kinases; RNA, Messenger; Signal Transduction; 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.

Topics: Acute-Phase Proteins; Amides; Analysis of Variance; Case-Control Studies; Dinoprost; Dinoprostone; Female; Humans; Intracellular Signaling Peptides and Proteins; Isoprostanes; Muscle, Smooth, Vascular; Pre-Eclampsia; Pregnancy; Protein Isoforms; Protein Serine-Threonine Kinases; Pyridines; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases; RNA, Messenger; Tissue Culture Techniques; Umbilical Arteries; Vasoconstrictor Agents