Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy.
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.
['Brewer|Justin|J|', 'Liu|Ruisheng|R|', 'Lu|Yan|Y|', 'Scott|Jeremy|J|', 'Wallace|Kedra|K|', 'Wallukat|Gerd|G|', 'Moseley|Janae|J|', 'Herse|Florian|F|', 'Dechend|Ralf|R|', 'Martin|James N|JN|', 'Lamarca|Babbette|B|']
D000804:Angiotensin II D000806:Angiotensin-Converting Enzyme Inhibitors D000818:Animals D001011:Aorta D001323:Autoantibodies D001794:Blood Pressure D004656:Enalapril D019332:Endothelin-1 D005260:Female D046110:Hypertension, Pregnancy-Induced D007668:Kidney D018384:Oxidative Stress D010920:Placenta D011225:Pre-Eclampsia D011247:Pregnancy D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D044140:Receptor, Angiotensin, Type 1
angiotensin II preeclampsia