High Dietary Protein Exacerbates Hypertension and Renal Damage in Dahl Salt‐Sensitive (SS) Rats by Increasing Infiltrating Immune Cells

Abstract

Experiments assessed the role of protein intake on salt sensitive hypertension in SS rats fed low (6%), normal (18%) or high (30%) protein diets. Increasing dietary NaCl from 0.4% to 4.0% for 3 weeks significantly increased mean arterial pressure (MAP) and albumin excretion rate (Ualb) in rats (n>6/group) fed the high protein diet (153 ± 7 mmHg and 114 ± 37 mg/day) when compared to rats fed normal (132 ± 3 mmHg and 26 ± 7 mg/day) or low protein diets (132 ± 6 mmHg and 4 ± 1 mg/day). Histological analysis demonstrated that high protein‐fed animals had significantly greater glomerular and tubular damage. Significantly greater numbers of infiltrating T‐lymphocytes were observed in kidneys of SS rats fed the high protein diet (18.9 ± 3 × 105cells/kidney) than in rats fed the low protein diet (9.1 ± 3 × 105 cells/kidney). Furthermore, treatment of SS rats fed the high protein diet with the immunosuppressant agent mycophenolate mofetil (20mg/kg/day) significantly reduced the number of infiltrating T cells in the kidneys by 44% while decreasing salt‐sensitive MAP by 16% and Ualb by 33%. These results indicate that dietary protein content is important for determining the degree of salt‐sensitive hypertension and kidney disease in SS rats; moreover, infiltrating T‐lymphocytes appear to play an important role in mediating the changes in blood pressure and kidney damage in these animals. Supported by HL29587 and DK062803.