Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy

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Item Type:	Article
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
Creators Name:	Brewer, J., Liu, R., Lu, Y., Scott, J., Wallace, K., Wallukat, G., Moseley, J., Herse, F., Dechend, R., Martin, J.N. and Lamarca, B.
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.
Keywords:	Angiotensin II, Preeclampsia, Animals, Rats
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	62
Number:	5
Page Range:	886-892
Date:	November 2013
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.113.01648
PubMed:	View item in PubMed

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