Abstract 132: Adrenergic Receptor Blockade Prevents Placental Ischemia-induced Hypertension

Hypertensive disorders of pregnancy are the number one cause of pregnancy-related deaths in the United States. Preeclampsia is a disorder of maternal hypertension and cardiovascular dysfunction typically presenting in the second half of pregnancy along with fetal growth restriction. There are no steadfast therapies besides early delivery of the fetus and ischemic placenta, which releases factors into the maternal circulation promoting hypertension. Although sympathetic nervous activity was found to be increased in preeclamptic versus normal pregnant women, it is unknown if sympathetic nervous system plays a role in placental ischemia-induced hypertension. To address this question, we tested the hypothesis that adrenergic receptor blockade prevents placental ischemia-induced hypertension. Wistar rats were randomized to receive reduced uterine perfusion pressure, (RUPP, n=6) or Sham (n=5) surgeries on gestational day 14 and examined at day 19. In RUPP vs Sham rats, respectively, mean arterial blood pressure (115 ± 4 vs 103 ±2 mmHg, P<0.05) and the number of absorbed fetuses (6 ± 1 vs 1 ± 1, P<0.05) were greater whereas average fetal weight was lower (1.7 ± 0.1 vs 2.0 ± 0.2, P<0.05) with similar placental weights (0.49 ± 0.03 vs 0.52 ± 0.03). In RUPP vs Sham rats, renal cortical norepinephrine content (HPLC) was higher (183 ± 15 vs 150 ± 8 pg/mg wet weight, P<0.05) and vasoconstriction to phenylephrine was greater in small, third order mesenteric arteries (Emax: 262 ± 19 vs 160 ± 26% of KCl response). A subset of RUPP rats (n=3) received terazosin and propranolol (3 mg/kg per day each, subcutaneous osmotic minipump) to block alpha- and beta-adrenergic receptors, respectively, beginning the day of RUPP surgery. At day 19, adrenergic blockade prevented the development of hypertension (100 ± 4 mmHg, P<0.05) and did not alter number of fetal absorptions (8 ± 1). Average fetal weight was higher (2 ± 0.1, P<0.05) and placental weight lower (0.41 ± 0.03, P<0.05) compared to the untreated RUPP rats. In conclusion, placental ischemia-induced hypertension depends on activation of the sympathetic nervous system. The mechanism for this enhanced sympathetic nerve activity is unknown but may involve factors released from the ischemic placenta.