Vascular endothelial growth factor decreases blood pressure in hypertensive pregnant rats

Abstract

We have recently shown that placental ischemia in the pregnant rat results in hypertension and elevated concentrations of circulating soluble fms‐like tyrosine kinase‐1 (sFlt‐1), a naturally occurring vascular endothelial growth factor (VEGF) antagonist that is over‐expressed in preeclampsia. We hypothesized that chronic VEGF administration during the last trimester of pregnancy would attenuate the hypertension associated with placental ischemia in our well characterized model of reduced uterine perfusion pressure (RUPP). VEGF (80 ug/kg/day) was administered for five days via osmotic mini‐pump placed intraperitoneal. Arterial pressure (AP) and tissues were obtained on gestation day 19 from RUPP+VEGF, RUPP and normal pregnant (NP) dams. VEGF administration attenuated the hypertension produced by RUPP (115 ± 1 vs. 135 ± 3 vs. 104 ± 1 mmHg; P < 0.001) but did not normalize AP to NP levels (mmHg; P < 0.01). VEGF ameliorated the fetal (1.9 ± 0.2 vs. 1.8 ± 0.1 vs.2.2 ± 0.1; P < 0.05) and placental (0.46 ± 0.12 vs. 0.36 ± 0.07 vs.0.57 ± 0.03; P < 0.05) growth restriction observed in RUPP compared to NP dams. These data demonstrate that VEGF may be an effective treatment for reducing high blood pressure associated with placental ischemia. Further, these results indicate that VEGF supplementation may also promote fetal and placental growth despite reductions in uterine perfusion pressure.