title: The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad.
abstract: Pregnancy demands major changes of the cardiovascular system, and this involves, among others, activation of the RAAS (renin-angiotensin-aldosterone system), allowing an aldosterone-dependent increase in volume. Remarkably, a relative resistance to the pressor response of AngII (angiotensin II) develops simultaneously to prevent the increase in blood pressure that would normally accompany RAAS activation. The increase in volume, the degree of RAAS activation and the diminished pressor response to AngII are less pronounced in pre-eclampsia. However, animal models displaying excessive RAAS activation also result in a pre-eclampsia-like syndrome, and the aldosterone/renin ratio is elevated in pre-eclampsia compared with a normal pregnancy. New insights into the pathogenesis of pre-eclampsia have revealed a major role for VEGF (vascular endothelial growth factor), VEGF-inactivating sFlt-1 (soluble fms-like tyrosine kinase-1) and AT1 (angiotensin II type 1) receptor autoantibodies. The last mentioned activate AT(1) receptors, thereby potentially suppressing circulating renin and aldosterone. VEGF, both directly and indirectly (by increasing capillary density), affects adrenal aldosterone synthesis. The present review summarizes all of the recent findings regarding RAAS regulation in pre-eclampsia compared with normal pregnancy, concluding that factors such as sFlt-1 and AT(1) receptor autoantibodies disturb the delicate balance that normally results in a volume increase and a diminished vasoconstrictor response to AngII in pregnant women. It is possible that there are non-parallel changes in the circulating and renal RAAS in pre-eclampsia, which are potentially reflected by the urinary levels of renin.
authors.affiliation: *Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Verdonk
authors.affiliation: †Department of Obstetrics and Gynecology, Division Obstetrics & Prenatal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Willy
authors.initials: W
authors.lastname: Visser
authors.affiliation: *Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Anton H
authors.initials: AH
authors.lastname: Van Den Meiracker
authors.affiliation: *Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000450:Aldosterone / Q000276:immunology / Q000502:physiology*; D000818:Animals; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000276:immunology / Q000503:physiopathology*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology / Q000502:physiology; D012084:Renin-Angiotensin System / Q000276:immunology / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000276:immunology / Q000502:physiology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000450:Aldosterone; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1