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Renal infiltration of T‐lymphocytes is associated with elevated intrarenal angiotensin II (AngII) and the development of hypertension and kidney damage in Dahl salt‐sensitive (SS) rats
Author(s) -
De Miguel Carmen,
Das Satarupa,
Lund Hayley,
Mattson David L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.805.5
Subject(s) - medicine , endocrinology , kidney , infiltration (hvac) , angiotensin ii , blood pressure , immune system , chemistry , immunology , physics , thermodynamics
This study examined mechanisms by which immune cells participate in hypertension and renal disease development in Dahl SS rats. Increasing dietary salt from low (LS, 0.4% NaCl) to high salt (4.0% NaCl, HS, n=7) significantly increased renal infiltration of T‐lymphocytes (from 8.8 ± 1.2 x 10 5 to 14.4 ± 2.0 x 10 5 cells/2 kidneys), increased arterial blood pressure (from 131±2 to165±6 mmHg), increased albumin excretion rate (from 17±3 to 129±20 mg/day), and resulted in renal glomerular and tubular damage. Furthermore, renal tissue AngII failed to suppress in SS rats on HS (LS: 133.7 ± 26.3 pg/g; HS: 134.1 ± 42.3 pg/g). Administration of the immunosuppressive agent mycophenolate mofetil (MMF; 20mg/kg/day) prevented the infiltration of T‐lymphocytes (HS/MMF: 5.4 ± 1.0 x 10 5 cells/2 kidneys vs. HS/Vehicle: 9.3 ± 1.5 x 10 5 cells/2 kidneys) and attenuated Dahl SS hypertension and renal disease. Of importance, rats treated with MMF demonstrated a suppression of renal tissue AngII (from 163.4 ± 25.7 to 87.7 ± 9.3 pg/g of tissue; n=6/each) when fed HS. Finally, infiltrating T‐cells contain renin activity (0.9 ± 0.8 ng AngI/ml/hr/10 6 cells, n=3). These data indicate that infiltrating T‐cells can participate in AngII production and are associated with increased intrarenal AngII, hypertension, and renal disease; suppression of T cell infiltration decreased AngII and prevented Dahl SS hypertension and kidney damage. Supported by HL‐29587.