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 (10 million) from the Dahl SS (SSCD247) rat, the SSp67phox/ rat (p67phoxCD247), or only PBS (PBSCD247) 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 SSCD247 rats compared with p67phoxCD247 and PBSCD247 rats. Interestingly, there was no difference between p67phoxCD247 and PBSCD247 rats in albuminuria or MAP after 21 days. The lack of CD3+ cells in PBSCD247 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 SSCD247 and p67phoxCD247 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.
Original language | English (US) |
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Pages (from-to) | F214-F223 |
Journal | American Journal of Physiology - Renal Physiology |
Volume | 325 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2023 |
Keywords
- NADPH oxidase
- T cells
- hypertension
- p67
- renal damage
ASJC Scopus subject areas
- Urology
- Physiology