Rag1-null Dahl SS rats reveal that adaptive immune mechanisms exacerbate high protein-induced hypertension and renal injury. Am J Physiol Regul Integr Comp Physiol 2018 Jul 01;315(1):R28-R35
Date
03/15/2018Pubmed ID
29537860Pubmed Central ID
PMC6087888DOI
10.1152/ajpregu.00201.2017Scopus ID
2-s2.0-85051255712 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
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.
Author List
Abais-Battad JM, Lund H, Fehrenbach DJ, Dasinger JH, Mattson DLMESH terms used to index this publication - Major topics in bold
Adaptive ImmunityAlbuminuria
Animals
B-Lymphocytes
Blood Pressure
CD3 Complex
Diet, High-Protein
Disease Models, Animal
Genes, RAG-1
Hypertension
Kidney
Kidney Diseases
Male
Rats, Inbred Dahl
Rats, Transgenic
Risk Factors
Sodium Chloride, Dietary
T-Lymphocytes
