Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep

Impaired materno-placental perfusion causes two important obstetric complications, fetal growth restriction and preeclampsia. This study investigated whether adenoviral vector-mediated overexpression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtAs) increases uterine artery blood flow (UBF). First-generation adenovirus vectors (5 × 10 11 particles) containing the VEGF gene (Ad.VEGF-A or -D) or the β-galactosidase reporter gene ( Ad.lacZ ) were injected into the UtAs of pregnant sheep ( n =6) at 88–102 days of gestation (term=145 days). UBF was measured using Doppler sonography before, and 4–7 days after injection. Mean UBF increased significantly from 233±156 (s.d.) ml min −1 to 753±415 ml min −1 following Ad.VEGF-A injection ( P =0.005, n =5); Ad.lacZ infection had no significant effect. Organ bath experiments on uterine arterial sections 4–7 days after injection showed that, compared with Ad.lacZ vessels, Ad.VEGF-A-transduced vessels had a reduced contractile response to phenylephrine (E max 148±10.9 vs E max 228.2±27.5, P