[PMID]: | 28461605 |
[Au] Autor: | Gao L; Zimmerman MC; Biswal S; Zucker IH |
[Ad] Endereço: | From the Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Nebraska Medical Center, Omaha (L.G., M.C.Z., I.H.Z.); and Department of Environmental Health and Engineering, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (S.B.). |
[Ti] Título: | Selective Gene Deletion in the Rostral Ventrolateral Medulla Evokes Hypertension and Sympathoexcitation in Mice. |
[So] Source: | Hypertension;69(6):1198-1206, 2017 06. |
[Is] ISSN: | 1524-4563 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional regulator of redox homeostasis that impacts antioxidant gene expression. Central oxidative stress and reduced antioxidant enzyme expression in the rostral ventrolateral medulla (RVLM) contributed to sympathoexcitation in chronic heart failure. In the current study, we hypothesized that deletion of Nrf2 in the RVLM would increase sympathetic drive and blood pressure. Experiments were performed in Nrf2-floxed mice treated with microinjection of lentiviral-Cre-GFP or lentiviral-GFP into the RVLM. Two weeks after viral administration, Nrf2 message, protein, oxidative stress, cardiovascular function, and sympathetic outflow were evaluated. We found that (1) Nrf2 mRNA and protein in the RVLM were significantly lower in Cre mice compared with control GFP mice. Nrf2-targeted antioxidant enzymes were downregulated, whereas reactive oxygen species were elevated. (2) Blood pressure measurements indicated that Cre mice displayed a significant increase in blood pressure (mean arterial pressure, 123.7±3.8 versus 100.2±2.2 mm Hg; <0.05, n=6), elevated urinary norepinephrine (NE) concentration (456.4±16.9 versus 356.5±19.9 ng/mL; <0.05, n=6), and decreased spontaneous baroreflex gain (up sequences, 1.66±0.17 versus 3.61±0.22 ms/mm Hg; <0.05, n=6; down sequences, 1.89±0.12 versus 2.98±0.19 ms/mm Hg; <0.05, n=6). (3) Cre mice displayed elevated baseline renal sympathetic nerve activity and impaired inducible baroreflex function. These data suggest that gene deletion in the RVLM elevates blood pressure, increases sympathetic outflow, and impairs baroreflex function potentially by impaired antioxidant enzyme expression. |
[Mh] Termos MeSH primário: |
Deleção de Genes Hipertensão/genética Bulbo/metabolismo Fator 2 Relacionado a NF-E2/genética Estresse Oxidativo/genética Sistema Nervoso Simpático/fisiopatologia
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[Mh] Termos MeSH secundário: |
Animais Antioxidantes/metabolismo Barorreflexo/fisiologia Determinação da Pressão Arterial/métodos Modelos Animais de Doenças Hipertensão Essencial Feminino Frequência Cardíaca/fisiologia Homeostase Hipertensão/fisiopatologia Masculino Camundongos Oxirredução RNA Mensageiro/análise Distribuição Aleatória Reação em Cadeia da Polimerase em Tempo Real/métodos Medição de Risco
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| 0 (Antioxidants); 0 (NF-E2-Related Factor 2); 0 (Nfe2l2 protein, mouse); 0 (RNA, Messenger) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 180113 |
[Lr] Data última revisão:
| 180113 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170503 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1161/HYPERTENSIONAHA.117.09123 |
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