title: Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Miguel
authors.forename: Chuanling
authors.initials: C
authors.lastname: Guo
authors.forename: Hayley
authors.initials: H
authors.lastname: Lund
authors.forename: Di
authors.initials: D
authors.lastname: Feng
authors.forename: David L
authors.initials: DL
authors.lastname: Mattson
mesh_terms: D000419:Albuminuria / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013113:Spin Labels; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D007166:Immunosuppressive Agents; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D019255:NADPH Oxidases; C001803:tempol; D016559:Tacrolimus