(859.4) Effects of pharmacologic interventions on hypertension attenuation and growth factors in animal model

Poster Board Number: E156

Ahmed Moustafa (University of MS Medical Center), Shauna-Kay Spencer (University of MS Medical Center), Teylor Bowles (University of MS Medical Center), Ashley Griffin (University of MS Medical Center), Kedra Wallace (University of Mississippi Medical Center)

Studies in hypertensive models of pregnancy have reported improvement in pregnancy outcomes and mean arterial pressure (MAP) after administration of various pharmacological agents. Circulating anti-angiogenic and placental growth factors are often used as biomarkers for placental dysfunction, however the effect of pharmacological intervention to reduce hypertension on placental function is still not clear. Therefore our objective was to determine if attenuation of hypertension during a hypertensive pregnancy is associated with an improvement in placental function. To address this question we used placentas that were collected from previous pharmacological studies and stored at -80°C. Timed-pregnant Sprague Dawley rats arrived on gestational day (GD) 11 and either remained normotensive (NP) or were implanted with a mini-osmotic pump on GD12 infusing sFlt-1 and sEng (4.7 amp; 7ug/kg respectively). Rats were treated with 5mg/kg ABT-627 (blockade of the ETA receptor), 5mg/kg Tempol (TEM, superoxide dismutase mimetic), 2mg/kg Orencia (T-cell depletion), 500ng/kg of MFL4 (neutralization of FasL) or 100pg/day IL-17 soluble RC (blockade of the IL-17) for variable times during pregnancy. On GD19 MAP was measured, pups were weighed and organs were stored for future use. Placentas (n=4-5) were homogenized and assayed in individual ELISAs for the following growth factors: sFlt-1, PlGF, VEGF and sEng. As expected pharmacological treatments significantly decreased MAP relative to hypertensive rats (p=0.005). When the placental sFlt-1/PlGF ratio was evaluated it was only significantly decreased in response to TEM (p=0.05). sEng was significantly decreased in rats receiving either Orencia (p=0.004) or IL-17RC (p=0.003). There were no statistically significant differences between hypertensive rats and treated rats in any other individual factors (pgt;0.05). Additionally, there was a negative correlation between MAP and pup weight (r=-0.24, p=0.03) and placental weight (r=-0.24, p=0.03). However there was not a significant positive correlation was found between MAP and the sFlt-1/PlGF ratio (r = 0.12, p=0.38).  Collectively these data indicate that while the selected pharmacological interventions were effective at lowering the blood pressure, the effect on growth factors associated with placental dysfunction was variable. In conclusion, the role of different pharmacological interventions on improving placental dysfunction remains unclear suggesting the need for further studies to evaluate the impact of other pharmacological interventions on placental dysfunction and pregnancy outcomes.