High dietary protein exacerbates hypertension and renal damage in Dahl SS rats by increasing infiltrating immune cells in the kidney

Abstract

The present study evaluated the influence and mechanism of action of dietary protein intake in Dahl SS hypertension and renal disease. Rats were fed isocaloric diets with low (6%), normal (18%), or high (30%) amounts of protein and 0.4% NaCl from 5 to 12 weeks of age; the NaCl content of the diets was then increased to 4.0% NaCl from 12 to 15 weeks of age. Rats fed the high-protein diet developed the highest mean arterial blood pressure and urine albumin-to-creatinine ratio when fed the 4.0% NaCl diet (153 ± 7 mm Hg and 8.0 ± 2.4, respectively) compared to rats fed normal protein (132 ± 3 mm Hg, 1.2 ± 0.3) or low-protein (132 ± 6 mm Hg, 0.3 ± 0.1) diets. Significantly greater numbers of infiltrating T lymphocytes were observed in kidneys of SS rats fed the high-protein diet (18.9 ± 3 × 10⁵ cells) than in rats fed the low-protein diet (9.1 ± 3 × 10⁵ cells). Furthermore, treatment of SS rats fed the high-protein diet with the immunosuppressant agent mycophenolate mofetil (20 mg/kg per day, ip) significantly reduced the number of infiltrating T cells in the kidneys (from 18.9 ± 2.7 to 10.6 ± 2.0 × 10⁵ cells) while decreasing blood pressure (from 133 ± 3 to 113 ± 4 mm Hg) and the albumin/creatinine ratio (from 10.9 ± 2.3 to 5.4 ± 1.2). These results demonstrate that restriction of protein intake protects the Dahl SS rats from hypertension and kidney disease and indicates that infiltrating immune cells play a pathological role in Dahl SS rats fed a high-protein diet. Moreover, the results show that hypertension in Dahl SS rats is sensitive to both NaCl and protein intake.

Figure 1

Mean arterial blood pressure (MAP, top) and urine albumin to creatinine excretion ratio (bottom) in SS/Mcw rats maintained on high, normal or low protein diets for 14 weeks. The measurements were made following 3 weeks on of a high NaCl (4.0%) diet. * indicates p<0.05 vs. the low protein diet group; † indicates p<.05 vs. the normal protein diet group.

Figure 2

Light microscopy images of representative glomeruli (40X original magnification, bottom panels) from kidneys obtained from male Dahl SS/Mcw rats fed the low protein or high protein diets. The lower panel illustrates changes in the glomerular injury score in rats fed the low, normal, or high protein diet. The NaCl content of each diet was increased from 0.4% to 4.0% for the final 3 weeks of the experiment. * indicates p<0.05 vs. the low protein diet group; † indicates p<.05 vs. the normal protein diet group.

Figure 3

Immunohistochemical localization of T cells in the renal cortex (Top Left) and medulla (Top Right) of Dahl SS rats fed 4.0% NaCl chow. T cells were localized in the renal tissue with antibodies directed against the cell surface marker CD43 (original magnification 20X). Bottom Left: Infiltrating T lymphocytes in the kidneys of Dahl SS/Mcw rats maintained on high or low protein diets for 14 weeks with 4.0% NaCl for the final three weeks. Bottom Right: Influence of vehicle or mycophenolate mofetil treatment (20 mg/kg/day, ip) during the high salt period on infiltrating T lymphocytes in the kidneys of Dahl SS/Mcw rats maintained on a high protein diet for 14 weeks with 4.0% NaCl for the final three weeks. * indicates p<0.05 vs. other group.

Figure 4

Influence of mycophenolate mofetil (20 mg/kg/day, ip) during the high salt period on mean arterial blood pressure (MAP, top) and urine albumin to creatinine excretion ratio (bottom) in SS/Mcw rats maintained on high low protein diets for 14 weeks with 4.0% NaCl administered for the final 3 weeks. * indicates p<0.05 vs. other group.