Rag1-null Dahl SS rats reveal that adaptive immune mechanisms exacerbate high protein-induced hypertension and renal injury

The present study, performed in Dahl salt-sensitive (SS) and SS-Rag1 (-/-) rats racking T and B lymphocytes, tested the hypothesis that immune cells amplify salt-sensitive hypertension and kidney damage in response to a high-protein diet. After being weaned, SS and SS-Rag1(-/-) rats were placed on an isocaloric, 0.4% NaCl diet containing normal (18%) or high (30%) protein. At 9 wk of age, rats were switched to a 4.0% NaCl diet containing the same amount of dietary protein and maintained on the high-salt diet for 3 wk. After being fed the high-salt diet, SS rats fed high protein had amplified hypertension and albumin excretion (158.7 +/- 2.6 mmHg and 140.8 +/- 16.0 mg/day, respectively, means +/- SE) compared with SS rats fed normal protein (139.4 +/- 3.6 mmHg and 69.4 +/- 11.3 mg/day). When compared with the SS rats, SS-Rag1(-/-) rats fed high protein were protected from exacerbated hypertension and albuminuria (142.9 +/- 5.8 mmHg and 66.2 +/- 10.8 mg/day). After 3 wk of the high-salt diet, there was a corresponding increase in total leukocyte infiltration (CD45(+)) in the kidneys of both strains fed high-protein diet. The SS-Rag1(-/-) rats fed high-protein diet had 74-86% fewer CD3(+) T lymphocytes and CD45R(+) B lymphocytes infiltrating the kidney versus SS rats, but there was no difference in the infiltration of CD11b/c(+) monocytes and macrophages, suggesting that the protective effects observed in the SS-Rag1(-/-) rats are specific to the reduction of lymphocytes. With the SS-Rag1(-/-) rats utilized as a novel tool to explore the effects of lymphocyte deficiency, these results provide evidence that adaptive immune mechanisms contribute to the exacerbation of salt-induced hypertension and renal injury mediated by increased dietary protein intake.