Influence of Parental Dietary Protein Source on Dahl Salt‐Sensitive Hypertension and Renal Disease
Authors: Abais‐Battad Justine M , Lund Hayley , Mattson David L 
Published: November 2023

Previous work in our laboratory has demonstrated the profound influence of the source of dietary protein in determining the severity of salt‐induced hypertension and renal injury in Dahl Salt‐Sensitive (SS) rats. Furthermore, recent studies have highlighted the importance of the maternal diet in determining the hypertensive phenotype of the offspring. Thus we hypothesized that maintaining Dahl SS breeders on a modified AIN‐76A diet that replaces the dietary protein source of casein for wheat gluten would protect the offspring from salt‐induced hypertension, renal damage, and renal inflammation. Proven SS breeders originally maintained on a 0.4% NaCl purified casein‐based AIN‐76A diet were switched to a modified custom diet containing an isocaloric substitution of wheat gluten for casein. The F1 offspring from the gluten breeders were weaned back to the 0.4% NaCl casein diet, isolating the difference between groups to the parental diet, then challenged with 3 weeks of 4.0% NaCl diet starting at 8 weeks of age. Blood pressure was measured via telemetry and urine was collected throughout the study to assess renal damage. At the end, renal immune cell infiltration was analyzed via flow cytometry and the kidneys assessed for histological damage. Additionally, a subset of F1 offspring were continued on the wheat gluten diet to serve as future breeders, where their offspring (F2 generation) were born of parents maintained on the gluten diet for their entire lives. The F2 offspring were also weaned to the 0.4% NaCl casein diet, challenged with 3 weeks of high salt diet, and subjected to the same measurements as the F1 generation. A trending attenuation in MAP was observed in F1 rats born from wheat gluten breeders versus those born from casein breeders when challenged with high salt. This was accompanied by a significant reduction in albuminuria (91.1±9.5 vs 207.5±25.3 mg/day, gluten vs casein, n=9) and outer medullary protein casting (7.4±0.8% vs 13.1±1.3%), suggesting that SS rats born from gluten breeders were protected from salt‐induced renal damage. This renal protection corresponded with a significant reduction in renal infiltration of CD45+ leukocytes (35.2% reduction), CD11b/c+ monocytes/macrophages (35.6%), CD3+ T cells (32.9%), and CD45R+ B cells (47.0%) in the offspring of gluten compared to casein‐fed breeders after 3 weeks of high salt. Upon analysis of the F2 rats born from breeders fed gluten their entire lives, these offspring demonstrated a significant attenuation in salt‐induced MAP elevation (141.5±1.5 vs 156.0±7.3 mmHg, gluten vs casein), albuminuria (74.4±14.7 vs 192.4±48.6 mg/day), and outer medullary protein casting (5.4±1.0% vs 9.2±1.6%) compared to rats born from casein breeders (n=7–9). However, unlike the F1 offspring, the F2 generation rats did not exhibit the expected reduction in renal immune cell infiltration. Although the cause for this discrepancy in renal inflammation in the F2 offspring remains to be further investigated, results from the F1 generation importantly demonstrated the influence of the parental diet during conception, gestation, and lactation in determining salt‐induced renal inflammation, hypertension, and renal damage in the offspring.Support or Funding InformationDK96859, HL116264, 15SFRN2391002, AHA16POST29900004