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

• Published in: American Journal of Physiology - Renal Physiology 2011-03, Vol.300 (3), p.F734-F742
• Main Authors: De Miguel, Carmen, Guo, Chuanling, Lund, Hayley, Feng, Di, Mattson, David L
• Format: Article
• Language: English
• Subjects: Albumin; Albuminuria - urine; Animals; Antioxidants - pharmacology; Cell Movement - drug effects; Cell Movement - physiology; Cells; Cyclic N-Oxides - pharmacology; Disease Models, Animal; Hypertension; Hypertension - metabolism; Hypertension - pathology; Hypertension - physiopathology; Immunosuppressive Agents - pharmacology; Kidney - metabolism; Kidney - pathology; Kidney - physiopathology; Kidney diseases; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidney Diseases - physiopathology; Lymphocytes; Male; NADPH Oxidases - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; Rats, Inbred Dahl; Rats, Sprague-Dawley; Rodents; Salt; Sodium Chloride, Dietary - pharmacology; Spin Labels; T cell receptors; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Tacrolimus - pharmacology
• ISSN: 1931-857X; 1522-1466; 0363-6127; 1522-1466
• DOI: 10.1152/ajprenal.00454.2010

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.