Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

Abstract

Studies published in Hypertension and other journals over the last few years have provided exciting new insights into potential mechanisms underlying the pathogenesis of hypertension during preeclampsia. Although numerous factors including genetic, immunologic, behavioral, and environmental influences have been implicated in the pathogenesis of preeclampsia, the main focus of this Hypertension Highlight is to review recent studies that link endothelial dysfunction and hypertension in preeclampsia.1–11 The pathophysiologic processes that underlie preeclampsia has been proposed to occur in 2 stages: stage 1, reduced placental perfusion, and stage 2, the maternal clinical syndrome.1,4 Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors that have profound effects on blood flow and arterial pressure regulation.1,4,10,11 These factors include a host of molecules such as the soluble VEGF receptor-1 (sFlt-1), the angiotensin II type-1 receptor autoantibody (AT1-AA), and cytokines such as tumor necrosis factor (TNF)-α which in turn generate widespread dysfunction of the maternal vascular endothelium.1–11 This dysfunction manifests as enhanced formation of factors such as endothelin, reactive oxygen species (ROS), thromboxane, 20-HETE, and augmented vascular sensitivity to angiotensin II.1–11 In addition, preeclampsia is also associated with decreased formation of vasodilators such as nitric oxide (NO) and prostacyclin.1–11 These alterations in vascular function not only lead to hypertension but multi-organ dysfunction, especially in women with early onset preeclampsia.1,4,11–20 Preterm preeclampsia remains a leading cause of maternal death and perinatal morbidity. Moreover, it has recently been recognized that women who endure preeclampsia are at a greater risk for cardiovascular disease later in life. Therefore, identifying the connection between placental ischemia/hypoxia and maternal cardiovascular abnormalities is an important area of investigation.1,10,11,21 In addition, the quantitative importance of the various endothelial and humoral factors that mediate vascular dysfunction and hypertension during preeclampsia remains to …