Effects of Parental Dietary Protein Source on Hypertension, Renal Injury, and Renal Inflammation

Recent studies from our laboratory have revealed an important role for the maternal diet as well as the dietary protein source in the development of salt‐induced hypertension and renal injury in Dahl Salt‐Sensitive (SS) rats. In response to salt, SS rats fed a grain diet are drastically protected from increases in blood pressure and albuminuria compared to SS rats fed a casein‐based diet. The current study sought to compare the hypertension and renal immune cell infiltration in offspring from parents consuming either a casein‐ or gluten‐based diet. Proven SS breeders originally maintained on a 0.4% NaCl casein‐based diet were switched to a modified diet containing an isocaloric protein substitution of wheat gluten for casein. We hypothesized that maintaining Dahl SS breeders on this modified 0.4% NaCl gluten‐containing diet would protect the offspring from salt‐induced hypertension, renal damage, and renal inflammation. All offspring, whether from casein‐ or gluten‐fed breeders, were weaned to the 0.4% NaCl casein diet, to isolate the difference between the two groups solely to the parental diet. Rats were instrumented with telemeters to record blood pressure, challenged with 3 weeks of 4.0% NaCl diet starting at 8 weeks of age, and had urine collected throughout the study to assess renal damage (n=7–10/group). At the end of the study, renal immune cell infiltration was analyzed via flow cytometry and the kidneys assessed for histological damage. After 3 weeks of high salt, there was a significant attenuation in mean arterial pressure (MAP) in the offspring from glutenfed breeders compared to the offspring from casein‐fed breeders (141.5±1.5 vs 156.0±7.3 mmHg, gluten vs casein). This protection was accompanied by a significant reduction in albuminuria (74.4±14.7 vs 192.4±48.6 mg/day, gluten vs casein) and proteinuria (149.1±21.0 vs 319.9±67.0 mg/day, gluten vs casein), while histological analysis demonstrated a decrease in outer medullary protein cast formation (5.4±1.0% vs 9.2±1.6%, gluten vs casein). Altogether, the offspring from the gluten breeders showed a distinct improvement in blood pressure, renal function, and renal morphology. However, upon analysis of the immune cells in the kidney, no differences were detected in the number of CD45+ total leukocytes, CD11b/c+ monocytes/macrophages, CD3+ T cells, and CD45R+ B cells. To examine potential differences in immune cell activation in the kidney, T cells isolated from the kidney were analyzed utilizing a PCR array approach. Of the 89 genes related to rat chemokines and chemokine receptors that were investigated, only two genes were significantly differentially expressed between T cells isolated from the kidneys of both groups. CMTM3 was upregulated (2.76‐fold change, p=0.04) and CMKLR1 was downregulated (2.99‐fold change, p=0.01) in the kidney T cells isolated from offspring of gluten breeders. While the specific role of these genes requires investigation with future studies, the current data demonstrate the influence of the parental diet in determining salt‐induced hypertension and renal damage in the offspring and indicate potential noteworthy genes that may play a crucial role in regulating the specific immune mechanisms leading to these differences in phenotype. Support or Funding Information DK96859, HL116264, 15SFRN2391002, 1F32HL136161 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .