Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease

Carmen de Miguel, Chuanling Guo, Hayley Lund, Di Feng, David L. Mattson

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

The present studies examined the role and mechanism of action of infiltrating T lymphocytes in the kidney during salt-sensitive hypertension. Infiltrating T lymphocytes in the Dahl salt-sensitive (SS) kidney significantly increased from 7.2 ± 1.8 × 105 cells/2 kidneys to 18.2 ± 3.9 × 105 cells/2 kidneys (n = 6/group) when dietary NaCl was increased from 0.4 to 4.0%. Furthermore, the expression of immunoreactive p67phox, gp91phox, and p47phox subunits of NADPH oxidase was increased in T cells isolated from the kidneys of rats fed 4.0% NaCl. The urinary excretion of thiobarbituric acid-reactive substances (TBARS; an index of oxidative stress) also increased from 367 ± 49 to 688 ± 92 nmol/day (n = 8/group) when NaCl intake was increased in Dahl SS rats. Studies were then performed on rats treated with a daily injection of vehicle (5% dextrose) or tacrolimus (0.25 mg·kg-1·day-1 ip), a calcineurin inhibitor that suppresses immune function, during the period of high-NaCl intake (n = 5/group). In contrast to the immune cell infiltration, increased NADPH oxidase expression, and elevated urine TBARS excretion in vehicle-treated Dahl SS fed high salt, these parameters were unaltered as NaCl intake was increased in Dahl SS rats administered tacrolimus. Moreover, tacrolimus treatment blunted high-salt mean arterial blood pressure and albumin excretion rate (152 ± 3 mmHg and 20 ± 9 mg/day, respectively) compared with values in dextrose-treated Dahl SS rats (171 ± 8 mmHg and 74 ± 28 mg/day). These experiments indicate that blockade of infiltrating immune cells is associated with decreased oxidative stress, an attenuation of hypertension, and a reduction of renal damage in Dahl SS rats fed high salt.

Original languageEnglish (US)
Pages (from-to)F734-F742
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number3
DOIs
StatePublished - Mar 1 2011

Keywords

  • Chronic renal insufficiency
  • Reactive oxygen species generation

ASJC Scopus subject areas

  • Physiology
  • Urology

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