Placental growth factor blunts uterine artery responses to angiotensin II.

ABSTRACT

OBJECTIVE: Changes in maternal serum concentration of placental growth factor (PlGF) and vascular response to intravascular infusion of Angiotensin II (Ang II) follow a bell-shaped curve pattern during gestation. This study evaluates the effects of PlGF and soluble vascular endothelial growth factor receptor-1 (sFlt-1) on responses of human uterine arteries (UA) to Ang II. DESIGN: Experimental. SETTING: Baylor College of Medicine and Texas Children's Hospital-Pavilion for Women. SAMPLE Uterine arteries samples (n = 14) were obtained from normotensive women undergoing caesarean hysterectomy at ≥32 weeks. METHODS: Uterine arteries rings were incubated with (1) Krebs solution; (2) PlGF at 1.45, 14.5, and 500 pg/ml; (3) sFlt-1 at 2 ng/ml; and (4) a combination of sFlt-1, and PlGF. Dose-contraction responses to Ang II were determined in UA rings incubated in the above-mentioned conditions. Responses were also measured in presence of L-NAME or inhibitors of endothelium-derived hyperpolarising factor apamine and charybdotoxin. The t-test was used for comparisons. MAIN OUTCOME MEASURE: Changes in vascular reactivity of UA rings. RESULTS: PlGF blunted (P = 0.03) and sFlt-1 increased (P <0.01) the UA maximum responses to Ang II. A combination of sFlt-1 and PlGF blunted UA responses to Ang II (P < 0.05). l-NAME, apamine, and charybdotoxin reversed the relaxation effects of PlGF on UA responses to Ang II (P < 0.05). CONCLUSIONS: PlGF contributes to the blunted vascular response to Angiotensin II during normotensive pregnancies and sFlt-1 appears to attenuate this effect. PlGF and sFlt-1 may contribute to the regulation of vascular tone during pregnancy by altering the vascular response to Angiotensin II. FUNDING: Baylor College of Medicine. TWEETABLE ABSTRACT Placental growth factor and soluble vascular endothelial growth factor receptor-1 modulate the uterine artery response to Angiotensin II in normotensive pregnant women.