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Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats - role of endothelin-1

Item Type:Article
Title:Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats - role of endothelin-1
Creators Name:Lamarca, B. and Parrish, M. and Ray, L.F. and Murphy, S.R. and Roberts, L. and Glover, P. and Wallukat, G. and Wenzel, K. and Cockrell, K. and Martin, J.N. and Ryan, M.J. and Dechend, R.
Abstract:Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and endothelin -1 (ET-1) are suggested to be important links between placental ischemia and hypertension during preeclampsia. Activation of the angiotensin II type 1 receptor (AT1R) increases endothelial cell production of ET-1; however, the importance of ET-1 in response to AT1-AA-mediated AT1 R activation during preeclampsia is unknown. Furthermore, the role of AT1-AA-mediated increases in blood pressure during pregnancy remains unclear. The objective of this study was to test the hypothesis that AT1-AA, increased to levels observed in preeclamptic women and placental ischemic rats, increases mean arterial pressure (MAP) by activation of the ET-1 system. Chronic infusion of purified rat AT1-AA into normal pregnant (NP) rats for 7 days increased AT1-AA from 0.68+/-0.5 to 10.88+/-1.1 chronotropic units (P<0.001). The increased AT1-AA increased MAP from 99+/-1 to 119+/-2 mm Hg (P<0.001). The hypertension was associated with significant increases in renal cortices (11-fold) and placental (4-fold) ET-1. To determine whether ET-1 mediates AT1-AA-induced hypertension, pregnant rats infused with AT1-AA and NP rats were treated with an ETA receptor antagonist. MAP was 100+/-1 mm Hg in AT1-AA+ETA antagonist-treated rats versus 98+/-2 mm Hg in ETA antagonist-treated rats. Collectively, these data support the hypothesis that one potential pathway whereby AT1-AAs increase blood pressure during pregnancy is by an ET-1-dependent mechanism.
Keywords:Preeclampsia, Hypertension, Kidney, Placenta, Inflammation, Animals, Rats
Publisher:American Heart Association
Page Range:905-909
Date:October 2009
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.109.137935
PubMed:View item in PubMed

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