Mycophenolate mofetil reduces renal T cell numbers and prevents high fat induced hypertension in Dahl rats

Abstract

Dahl salt-sensitive rats (SS) display fat-sensitive hypertension following 4 weeks of high fat diet (HF; 60% fat/0.4% NaCl) compared to SS on normal fat diet (NF; 14% fat/0.4% NaCl) (telemetry: 152 ± 5 vs 133 ± 6 mmHg; p<0.05; n=4). Recently, we showed that mycophenolate mofetil (MMF; 30 mg/kg/day) prevents fat-induced hypertension. The aims of this study were to determine if 1: HF increases renal T cell number vs NF SS; 2: MMF reduces renal T cell numbers in HF SS; 3: MMF reduces total cellular proliferation in kidneys from HF SS. Following magnetic-cell separation, renal T lymphocytes were not changed (p>0.05) with HF in SS (HF: 22 ± 2; NF: 33 ± 6 × 106/2 kidneys; n=3). With immunolocalization, CD3+ cell count was not altered (p>0.05) with HF in renal cortex (HF: 16 ± 3; NF: 17 ± 3 cells/400 μm2; n=6–8) or medulla (HF: 25 ± 2; NF: 20 ± 2 cells/400 μm2; n=6–8). MMF reduced renal cortical CD3+ cells in HF SS (28 ± 3 vs 16 ± 3 cells/400 μm2; n=5; p<0.05) but not medullary CD3+ counts (HF-MMF: 19 ± 2 vs HF+MMF: 16 ± 3; n=5; p>0.05). Total cellular proliferation status was assessed with Ki-67 immunhistochemistry. MMF treatment did not change (p>0.05) renal cortical Ki-67+ cells (HF-MMF: 16 ± 1; HF+MMF: 15 ± 2 Ki-67+ cells/400 μm2; n=5) or medullary Ki-67+ cells (HF-MMF: 19 ± 2; HF+MMF: 21 ± 6 Ki-67+ cells/400 μm2; n=5). These data suggest that immunosuppression prevents hypertension in HF SS by reducing renal T lymphocyte number.