Preeclampsia (PE) is a pregnancy-related hypertensive disorder (HTN-Preg) with unclear mechanism. Imbalance between anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic placental growth factor (PlGF) has been observed in PE, but the vascular targets and signaling pathways involved are unclear. We tested if inducing sFlt-1/PlGF imbalance by infusing sFlt-1 (10 µg/kg/day) in pregnant (Preg) rats increases BP and vascular reactivity; and if restoring sFlt-1/PlGF balance by infusing PIGF (20 µg/kg/day) in a rat model of reduced uterine perfusion pressure (RUPP) improves BP and vascular function. On gestation day 19, BP was in Preg+sFlt-1 and RUPP>Preg and in RUPP+PlGF<RUPP. Plasma sFlt-1/PlGF ratio was increased in Preg+sFlt-1 and RUPP, and was reduced in RUPP+PlGF rats. In endothelium-intact aorta, carotid, mesenteric and renal artery, pheylephrine (Phe) and high KCl-induced contraction was in Preg+sFlt-1 and RUPP>Preg and RUPP+PlGF. The differences in vascular reactivity between groups were less apparent in vessels treated with NOS inhibitor L-NAME or guanylate cyclase inhibitor ODQ or endothelium-denuded, suggesting changes in endothelial NO-cGMP. Acetylcholine (ACh)-induced relaxation was in Preg+sFlt-1 and RUPP<Preg and RUPP+PlGF, and was blocked by L-NAME, ODQ or endothelium-removal. Aortic total eNOS and phospho-eNOS were in Preg+sFlt-1 and RUPP<Preg and RUPP+PlGF. ACh-induced vascular nitrate/nitrite production was in Preg+sFlt-1 and RUPP<Preg and RUPP+PlGF. Vascular relaxation to sodium nitroprusside was not different among groups. Thus, a tilt in angiogenic/anti-angiogenic balance towards sFlt-1 is associated with decreased vascular relaxation via NO-cGMP and increased vasoconstriction and BP. Restoring angiogenic/anti-angiogenic balance using PlGF enhances vascular relaxation and decreases vasoconstriction and BP in HTN-Preg.