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

Justine M. Abais-Battad, Hayley Lund, Daniel J. Fehrenbach, John Henry Dasinger, David L. Mattson

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The present study, performed in Dahl salt-sensitive (SS) and SS-Rag1-/- rats lacking 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.

Original languageEnglish (US)
Pages (from-to)R28-R35,
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number1
StatePublished - Jul 2 2018
Externally publishedYes


  • Dietary protein
  • Kidney disease
  • Salt-sensitive hypertension
  • T lymphocytes

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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