title: Role of the renin-angiotensin system in the pathogenesis of preeclampsia.
abstract: 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 B(2) receptor heterodimerization and the production of an autoantibody against AT(1). 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.
authors.affiliation: Univ. of Wisconsin Medical School, Dept. of Obstetrics and Gynecology, 202 S. Park Str., Madison, WI 53715, USA. dmshah@wisc.edu
authors.forename: Dinesh M
authors.initials: DM
authors.lastname: Shah
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000209:etiology* / Q000503:physiopathology*; D011247:Pregnancy; D012084:Renin-Angiotensin System / Q000502:physiology*