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Hypertension in response to placental ischemia during pregnancy: role of B lymphocytes

Item Type:Article
Title:Hypertension in response to placental ischemia during pregnancy: role of B lymphocytes
Creators Name:Lamarca, B. and Wallace, K. and Herse, F. and Wallukat, G. and Martin, J.N. and Weimer, A. and Dechend, R.
Abstract:Preeclampsia is associated with innate inflammatory response resulting in elevated tumor necrosis factor-alpha, agonistic autoantibodies to the angiotensin II type I receptor, and activation of endothelin 1 (ET-1). This study was designed to determine the role of B-cell depletion, resulting in agonistic autoantibodies to the angiotensin II type I receptor suppression to mediate hypertension via activation of ET-1 in the placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. To achieve this goal we examined the effect of RUPP on mean arterial pressure and ET-1 in the presence and absence of chronically infused rituximab (R; 250 mg/kg), a B-lymphocyte-suppressive agent used clinically to treat autoimmune diseases. Mean arterial pressure was 103+/-1 mm Hg in normal pregnant (NP) rats; 103+/-3 mm Hg in NP+R versus 133+/-2 mm Hg in RUPP rats, and 118+/-2 mm Hg in RUPP+R rats (P<0.001 vs RUPP controls). B lymphocytes decreased from 6.0+/-0.5% gated cells in RUPP to 3.7+/-0.8% gated cells in RUPPbR rats. Importantly, agonistic autoantibodies to the angiotensin II type I receptor decreased from 18+/-1 bpm in RUPP rats to 10+/-1 bpm in RUPPbR rats. ET-1 decreased 1.5-fold in kidneys and 4-fold in the placenta (P<0.01) of RUPP+R versus RUPP rats. Media ET-1 excretion from endothelial cells exposed to serum from NP, RUPP, NP+R, or RUPP+R rats was determined. ET-1 from endothelial cells treated with NP serum was 53+13 pg/mg and increased to 75+10 pg/mg with RUPP serum. In contrast, ET-1 secretion decreased in response to B-cell-depleted RUPP serum to 50+/-8 pg/mg and was unchanged in response to NP+R sera (46+/-12 pg/mg). These data demonstrate the important roles that B-lymphocyte activation and agonistic autoantibodies to the angiotensin II type I receptors play in the pathophysiology of hypertension in response to placental ischemia.
Keywords:Hypertension, Inflammation, Renin-Angiotensin System, Pregnancy, Endothelin, Animals, Rats
Source:Hypertension
ISSN:0194-911X
Publisher:American Heart Association (U.S.A.)
Volume:57
Number:4
Page Range:865-871
Date:April 2011
Official Publication:https://doi.org/10.1161/HYPERTENSIONAHA.110.167569
PubMed:View item in PubMed

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