Administration of the PARP inhibitor Pj34 ameliorates the impaired vascular function associated with eNOS(-/-) mice.

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.