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

Am J Physiol Renal Physiol. 2011 Mar;300(3):F734-42. doi: 10.1152/ajprenal.00454.2010. Epub 2010 Dec 15.

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 × 10(5) cells/2 kidneys to 18.2 ± 3.9 × 10(5) cells/2 kidneys (n = 6/group) when dietary NaCl was increased from 0.4 to 4.0%. Furthermore, the expression of immunoreactive p67(phox), gp91(phox), and p47(phox) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albuminuria / urine
  • Animals
  • Antioxidants / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cyclic N-Oxides / pharmacology
  • Disease Models, Animal
  • Hypertension / metabolism
  • Hypertension / pathology
  • Hypertension / physiopathology*
  • Immunosuppressive Agents / pharmacology
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney / physiopathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology*
  • Male
  • NADPH Oxidases / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Inbred Dahl
  • Rats, Sprague-Dawley
  • Sodium Chloride, Dietary / pharmacology
  • Spin Labels
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology*
  • Tacrolimus / pharmacology

Substances

  • Antioxidants
  • Cyclic N-Oxides
  • Immunosuppressive Agents
  • Sodium Chloride, Dietary
  • Spin Labels
  • NADPH Oxidases
  • tempol
  • Tacrolimus