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Shah, Dinesh M. Role of the renin-angiotensin system in the pathogenesis of preeclampsia. Am J Physiol Renal Physiol 288: F614 -F625, 2005; doi:10.1152/ ajprenal.00410.2003.-Preeclampsia is a hypertensive disorder unique to pregnancy with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression observed both in human preeclampsia and in a transgenic mouse model with a human preeclampsia-like syndrome supports the concept that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. A novel disease paradigm of the two-kidney one-clip (2K-1C) Goldblatt model is presented for preeclampsia, wherein the gravid uterus is the clipped "kidney" and the two maternal kidneys represent the unclipped kidney. Validation of the 2K-1C Goldblatt model analogy requires evidence of elevated angiotensin II in the peripheral circulation before vascular maladaptation in preeclampsia. Convincing evidence of the elevation of angiotensin II in preeclampsia does not exist despite the fact that much of vascular pathogenesis appears to be due to angiotensin type I (AT 1) receptor activation. Vascular maladaptation with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT 1 and bradykinin B2 receptor heterodimerization and the production of an autoantibody against AT1. Various organ systems with a predilection for involvement in preeclampsia are each a site of a tissue-based RAS. How angiotensin II-mediated mechanisms may explain the primary clinical-pathological features of preeclampsia is described. Future investigations are proposed to more precisely define the role of activation of the uteroplacental RAS in the mechanisms underlying preeclampsia.HYPERTENSIVE DISORDERS COMPLICATE approximately 5-7% of all pregnancies (35a). These disorders include 1) chronic hypertension of whatever origin, including essential hypertension and chronic renal disease; 2) gestational hypertension, a hypertensive disorder occurring in pregnancy without multisystem involvement; 3) preeclampsia syndrome superimposed on chronic hypertension; 4) preeclampsia syndrome occurring de novo and only in the first pregnancy; and 5) preeclampsia syndrome occurring in a subsequent pregnancy and/or recurring with an underlying susceptibility state.Preeclampsia is a unique syndrome of pregnancy characterized by hypertension, proteinuria, and, frequently, edema. Several pathophysiological mechanisms have been implicated in the development of preeclampsia. These include endothelial dysfunction (36), an inflammatory p...

Preeclampsia is a hypertensive disorder that is unique to pregnancy, with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression in human preeclampsia and in transgenic mouse models with a human preeclampsia-like syndrome shows that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. Vascular maladaptation in preeclampsia with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms through angiotensin receptor type I (AT1) activation. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT1 and bradykinin B2 receptor heterodimerization and the production of autoantibody against AT1. Various organ systems with predilection for involvement in preeclampsia are sites of tissue-based RAS. Angiotensin II-mediated mechanisms may explain the primary clinicopathologic features of preeclampsia. In this review, these various aspects are critically examined and an integrated concept on the role of RAS in preeclampsia is presented.

Despite lack of evidence for effectiveness, obstetricians in the United States prescribe antepartum bed rest for more than 700,000 women per year. However, in nonpregnant samples, bed rest treatment produces weight loss. This study assessed maternal weight change (gain) during antepartum hospitalization for bed rest treatment; compared appropriateness of infant birth weights for gestational age, race, and gender; and determined whether maternal weight change predicted infant birth weight. The convenience sample for this longitudinal study consisted of 141 women with high-risk pregnancies who were treated with hospital bed rest. Weekly rate of pregnancy weight change by body mass index was compared with Institute of Medicine recommendations for rate of pregnancy weight gain. Infant birth weight was compared with current US infant birth weights for matching gestational age, gender, and race. Weekly antepartum weight change was significantly lower than Institute of Medicine recommendations (P < 0.001). Infant birth weights were also significantly lower than the national mean when matched for each infant's gestational age, race, and gender (P < 0.001). Maternal weight change predicted infant birth weight (P = 0.05). Bed rest treatment is ineffective for improving pregnancy weight gain. Lower infant birth weights across all gestational ages suggest that maternal weight loss during bed rest may be associated with an increased risk of fetal growth restriction. A randomized trial comparing women with high-risk pregnancies who are ambulatory with those on bed rest is needed to determine whether bed rest treatment, underlying maternal-fetal disease, or both influence inadequate maternal weight gain and poor intrauterine growth.