title: Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy.
abstract: Hypertension during preeclampsia is associated with increased maternal vascular sensitivity to angiotensin II (ANGII). This study was designed to determine mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA) enhance blood pressure (mean arterial pressure [MAP]) and renal vascular sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery resistance index in response to chronic administration of ANGII or AT1-AA or AT1-AA+ANGII in pregnant rats compared with control pregnant rats. To examine mechanisms of heightened sensitivity in response to AT1-AA during pregnancy, we examined the role of endogenous ANGII in AT1-AA-infused pregnant rats, and that of endothelin-1 and oxidative stress in AT1-AA+ANGII-treated rats. Chronic ANGII increased MAP from 95±2 in normal pregnant rats to 115±2 mm Hg; chronic AT1-AA increased MAP to 118±1 mm Hg in normal pregnant rats, which further increased to 123±2 mm Hg with AT1-AA+ANGII. Increasing ANGII from 10(-11) to 10(-8) decreased afferent arteriole diameter from 15% to 20% but sharply decreased afferent arteriole diameter to 60% in AT1-AA-pretreated vessels. Renal artery resistance index increased from 0.67 in normal pregnant rats to 0.70 with AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA+ANGII-infused rats. AT1-AA-induced hypertension decreased with enalapril but was not attenuated. Both tissue endothelin-1 and reactive oxygen species increased with AT1-AA+ANGII compared with AT1-AA alone, and blockade of either of these pathways had significant effects on MAP or renal artery resistance index. These data support the hypothesis that AT1-AA, via activation of endothelin-1 and oxidative stress and interaction with endogenous ANGII, is an important mechanism whereby MAP and renal vascular responses are enhanced during preeclampsia.
authors.affiliation: Department of Pharmacology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216. bblamarca@umc.edu.
authors.forename: Justin
authors.initials: J
authors.lastname: Brewer
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Jeremy
authors.initials: J
authors.lastname: Scott
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.forename: Gerd
authors.initials: G
authors.lastname: Wallukat
authors.forename: Janae
authors.initials: J
authors.lastname: Moseley
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.forename: James N
authors.initials: JN
authors.lastname: Martin
authors.forename: Babbette
authors.initials: B
authors.lastname: Lamarca
mesh_terms: D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D004656:Enalapril / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D046110:Hypertension, Pregnancy-Induced / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010920:Placenta / Q000378:metabolism / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001323:Autoantibodies; D019332:Endothelin-1; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D004656:Enalapril
keywords: angiotensin II; preeclampsia
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