Aminoimidazole carboxamide ribonucleotide administration attenuates placental‐ischemia‐induced hypertension and angiogenic imbalance in rats

Abstract

Previous studies suggest restoration of angiogenic balance can lower blood pressure and improve vascular endothelial cell function in several experimental models of preeclampsia. Stimulation of the adenosine monophosphate kinase (AMPK) pathway has previously been shown to increase vascular endothelial growth factor (VEGF) expression. We hypothesized stimulation of AMPK with aminoimidazole carboxamide ribonucleotide (AICAR) would increase plasma VEGF and attenuate reduced utero‐placental perfusion pressure (RUPP)‐induced hypertension. RUPP was induced on day 14 of gestation (term=21) by introducing silver clips on the inferior abdominal aorta and ovarian arteries. AICAR was administered i.p. (50mg/kg) twice daily from day 14–18, and mean arterial pressure (MAP) and tissues were collected on day 19. Placental phosphorylated‐AMPKα:AMPKα was increased in RUPP+AICAR vs. normal pregnant (NP) and RUPP (0.48±0.06 vs. 0.17±0.01 vs. 0.25±0.06; P<0.05). AICAR also increased plasma VEGF in the RUPP+AICAR vs. RUPP (NP 843±52; RUPP 420±75; NP+AICAR 708±179; RUPP+AICAR 884±128 pg/ml; P<0.05). Lastly, RUPP hypertension was mitigated by AICAR infusion (NP 95±3; RUPP 123±2; NP+AICAR 104±3; RUPP+AICAR 101±5mmHg; P<0.05). These findings suggest pharmacological activation of the AMPK pathway may be useful to restore angiogenic balance and lower blood pressure in hypertensive pregnancies.