title: Administration of the PARP inhibitor Pj34 ameliorates the impaired vascular function associated with eNOS(-/-) mice.
abstract: A low-resistance/high-flow uteroplacental circulation is integral to a healthy pregnancy. Impaired flow in the uterine circulation is associated with intrauterine growth restriction (IUGR) and preeclampsia (PE). Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which has been associated with oxidative stress-induced vascular dysfunction. Using the endothelial nitric oxide synthase (eNOS(-/ -)) knockout mouse model, which features vascular dysfunction and IUGR, we tested the hypothesis that administration of a PARP inhibitor may ameliorate the vascular dysfunction associated with the eNOS(-/-) model. eNOS(-/-) animals were characterized by impaired uterine artery function when compared to controls. Administration of the PARP inhibitor PJ34 prevented this dysfunction. Gestational day (GD) 17.5 eNOS(-/-) mice did not exhibit altered systolic blood pressure when compared to control mice. However, treatment of eNOS(-/-) mice with PJ34 significantly reduced systolic blood pressure when compared to vehicle-treated eNOS(-/-). Administration of a PARP inhibitor protects uterine artery function in the face of eNOS(-/-) deficiency.
authors.affiliation: Anu Research Centre, University College Cork, Cork, Ireland. fred@umail.ucc.ie
authors.forename: Fred A
authors.initials: FA
authors.lastname: English
authors.forename: Fergus P
authors.initials: FP
authors.lastname: McCarthy
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Andersson
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Stanley
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Walsh
authors.forename: Louise C
authors.initials: LC
authors.lastname: Kenny
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D005865:Gestational Age; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D055988:Uterine Artery / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D052250:Nitric Oxide Synthase Type III