Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.
Am J Physiol Renal Physiol
; 325(2): F214-F223, 2023 08 01.
Article
em En
| MEDLINE
| ID: mdl-37318993
ABSTRACT
Infiltrating T cells in the kidney amplify salt-sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells (SSCD247-/-) or of the p67phox subunit of NADPH oxidase 2 (NOX2; SSp67phox-/-) attenuates SS hypertension in the Dahl SS rat. We hypothesized that reactive oxygen species produced by NOX2 in T cells drive the SS phenotype and renal damage. T cells were reconstituted by adoptively transferring splenocytes (â¼10 million) from the Dahl SS (SSâCD247) rat, the SSp67phox-/- rat (p67phoxâCD247), or only PBS (PBSâCD247) into the SSCD247-/- rat on postnatal day 5. Animals were instrumented with radiotelemeters and studied at 8 wk of age. There were no detectable differences in mean arterial pressure (MAP) or albuminuria between groups when rats were maintained on a low-salt (0.4% NaCl) diet. After 21 days of high-salt diet (4.0% NaCl), MAP and albuminuria were significantly greater in SSâCD247 rats compared with p67phoxâCD247 and PBSâCD247 rats. Interestingly, there was no difference between p67phoxâCD247 and PBSâCD247 rats in albuminuria or MAP after 21 days. The lack of CD3+ cells in PBSâCD247 rats and the presence of CD3+ cells in rats that received the T cell transfer demonstrated the effectiveness of the adoptive transfer. No differences in the number of CD3+, CD4+, or CD8+ cells were observed in the kidneys of SSâCD247 and p67phoxâCD247 rats. These results indicate that reactive oxygen species produced by NOX2 in T cells participates in the amplification of SS hypertension and renal damage.NEW & NOTEWORTHY Our current work used the adoptive transfer of T cells that lack functional NADPH oxidase 2 into a genetically T cell-deficient Dahl salt-sensitive (SS) rat model. The results demonstrated that reactive oxygen species produced by NADPH oxidase 2 in T cells participate in the amplification of SS hypertension and associated renal damage and identifies a potential mechanism that exacerbates the salt-sensitive phenotype.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cloreto de Sódio
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Hipertensão
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Ano de publicação:
2023
Tipo de documento:
Article