Renin angiotensin signaling in normal pregnancy and preeclampsia.

Many reports indicate that there is an increase in almost all of the components of the renin-angiotensin system (RAS) during an uncomplicated pregnancy, but renin activity, angiotensin II, and aldosterone decrease in preeclampsia (PE) for reasons that are unclear. PE is a life-threatening disorder of late pregnancy characterized by hypertension, proteinuria, increased soluble fms-like tyrosine kinase-1, as well as renal and placental morphologic abnormalities. Although a leading cause of maternal and perinatal morbidity and mortality, the pathogenic mechanisms of PE remain largely undefined. Immunologic mechanisms and aberrations of the RAS have been long considered contributors to the disorder. Bridging these two concepts, numerous studies report the presence of the angiotensin II type I receptor agonistic autoantibody (AT(1)-AA) found circulating in preeclamptic women. This autoantibody induces many key features of the disorder through AT(1) receptor signaling, and has been implicated in the pathogenesis of PE. Here we review the functions of the RAS during normal pregnancy and PE, and highlight the role of AT(1)-AA in both animal models and in the human disorder.