| [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
|
| [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
|
| [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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