Novel Modalities for Preeclampsia Prevention: A Role for Exercise Training and 5–Aminoimidazole–4–Carboxamide–1–β–D–Ribofuranoside (AICAR) Administration
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Preeclampsia (PE) remains one of the most enigmatic and pervasive conditions developed during pregnancy and is a leading cause of maternal and fetal morbidity and mortality throughout the world. Afflicting nearly 5-8% of pregnancies in the Unites States, PE is most commonly characterized by an increase in blood pressure and high protein excretion near or after the 20th week of gestation. Unfortunately, few effective treatments are available, and the only "cure" is delivery. While the molecular pathogenesis of PE remains undefined, an interruption in placental blood flow, or placental ischemia, is widely observed as a primary contributor to the syndrome progression. Furthermore, to investigate the role of both pharmacological and non-pharmacological modalities to prevent placental ischemia induced hypertension, we employed a robust model of reduced utero-placental perfusion pressure (RUPP) in the pregnant rat. First, in Chapter IV, exercise initiated during gestation was not effective in the prevention of RUPP-induced hypertension, whereas exercise training prior to and continued through gestation prevented the increase in blood pressure. Though the molecular contributions to this effect are undefined, the effects appear to be independent of angiogenic balance restoration. Finally, in Chapter V, administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) was explored as a novel pharmacological modality to prevent the onset of hypertension and endothelial dysfunction in the RUPP model. As hypothesized, AICAR ameliorated the RUPP-induced hypertension, and the anti-hypertensive effect in the RUPP appears to be dependent on the restoration of angiogenic balance in the maternal plasma. This dissertation includes previously published and unpublished co-authored material.