The role of RAS in the pathogenesis of preeclampsia

Abstract

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.

Hyperuricemia, Cardiovascular Disease, and the Metabolic Syndrome: Figure 1.

“…Additionally, water loading (the provision of large volumes of water prior to study participation) is associated with an increase in fractional clearance of UA 8 , and in this situation, the RAS is less active. Further, autoimmune stimulation of angiotensin II receptors (AT1 receptors) is implicated in the pathophysiology of preeclampsia, a condition that also presents with elevated serum UA concentrations 9 . Therefore, we hypothesize that in obese individuals, excess angiotensin II activity causes a sustained reduction in the fractional clearance of UA, which leads to chronic retention of UA and thus hyperuricemia.…”

Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis

“…AGT, the precursor of angiotensin peptides, is cleaved to angiotensin I by renin, and then Angiotensin I is converted into bioactive angiotensin II by ACE, which is the major enzyme of RAS [5]. ACE I/D (rs4646994) and AGT M235T (rs699) are two of the most frequently investigated RAS related gene polymorphisms.…”

Etiopathogenesis of hypertension in pregnant women

“…RAAS jest to układ hormonalno-enzymatyczny regulujący stężenie jonów sodowych i potasowych oraz objętość krwi krążącej. Zwiększona aktywacja tego układu w łożysku może tłumaczyć ogólne zaburzenia regulacji naczyniowej obserwowane w stanie przedrzucawkowym, takie jak nadciśnienie, dysfunkcje śródbłonka naczyniowego, zwiększona wrażliwość naczyń na działanie angiotensyny [42]. Angiotensyna II jest oktapeptydem, wykazującym silne działanie wazokonstrykcyjne po zwią-zaniu się z receptorem dla angiotensyny II typu 1 (AT 1) [43].…”