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Am J Hypertens ; 33(6): 514-519, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31713584

RESUMO

BACKGROUND: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). We demonstrated that MBG induces fibrosis via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. We hypothesized that PE blockade of increased MBG with antibody would lessen the fibrosis of umbilical arteries and lower the blood pressure in rats with PE. METHODS: We tested 36 pregnant Sprague-Dawley rats in which 12 were made hypertensive by 1.8% Na supplementation (days 6-19 of gestation), 12 pregnant rats served controls. At day 19, PE rats received one intraperitoneal injection of polyclonal anti-MBG-4 antibody (0.5 ug/ml) for 4 hours. RESULTS: PE was associated with higher blood pressure (117 ± 2 vs. 107 ± 2 mm Hg; P < 0.01), plasma MBG levels (1.54 ± 0.34 vs. 0.49 ± 0.11 nmol/L; P < 0.01), protein excretion (26 vs. 12 mg/24 hours), sFlt-1 (3-fold), decrease in Fli1 (7-fold) and increase in collagen-1 in aorta (4-fold) vs. control rats (all P < 0.01). In 12 rats treated with polyclonal anti-MBG-4 antibody blood pressure dropped (93 ± 3 mm Hg) and Fli1 was decreased much less (2-fold; P < 0.01 vs. nontreated rats). CONCLUSIONS: These results demonstrate that in experimental PE elevated MBG level is implicated in umbilical fibrosis via suppression of Fli1.


Assuntos
Anticorpos/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Bufanolídeos/antagonistas & inibidores , Pré-Eclâmpsia/prevenção & controle , Proteína Proto-Oncogênica c-fli-1/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Artérias Umbilicais/efeitos dos fármacos , Animais , Bufanolídeos/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose , Pré-Eclâmpsia/enzimologia , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Ratos Sprague-Dawley , Cloreto de Sódio na Dieta , Artérias Umbilicais/enzimologia , Artérias Umbilicais/patologia , Artérias Umbilicais/fisiopatologia , Regulação para Cima
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