Pathophysiology of Hypertension in Preeclampsia: A Lesson in Integrative Physiology

摘要

Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia has yet to be fully elucidated. However, it is evident that this is a complex disorder involving multiple organ systems and, by using integrative approaches, enormous progress has been made towards understanding the pathophysiology of preeclampsia. Growing evidence supports the concept that the placenta plays a central role in the pathogenesis of preeclampsia and that reduced uteroplacental perfusion, which develops as a result of abnormal cytotrophoblast invasion of spiral arterioles, triggers the cascade of events leading to the maternal disorder. Placental ischemia leads to release of soluble placental factors, many of which are classified as anti-angiogenic or pro-inflammatory. Once these ischemic placental factors reach the maternal circulation, they cause widespread activation and dysfunction of the maternal vascular endothelium that results in enhanced formation of endothelin-1 and superoxide, increased vascular sensitivity to angiotensin II, and decreased formation of vasodilators such as nitric oxide. This review highlights these links between placental ischemia, maternal endothelial activation, and renal dysfunction in the pathogenesis of hypertension in preeclampsia.