Renal Response to Dietary Salt in High Sodium Lithium Countertransport (SLC) Baboons

Abstract

Aim: To identify genes and pathways that regulate SLC activity, a marker for essential hypertension, we challenged normal (N) and high (H) SLC baboons with a high salt (HS) diet and compared renal transcriptome profiles.Study design: NSLC (256 ± 9) and HSLC (426 ± 17) baboons (n = 5/group) were fed a low salt diet (20 mmol/day NaCl) for 8 weeks then fed a HS diet (150 mmol/day NaCl) for 6 weeks. Kidney biopsy transcriptome data from each diet were used for pairwise, cluster and pathway analyses.Results: Analysis of HSLC vs NSLC baboons on HS showed differential expression of 8.2% of expressed genes with 148 genes up‐ and 817 genes down‐regulated [including 10 solute carrier family genes]. Eight KEGG pathways were up‐ and 32 KEGG pathways were down‐regulated including oxidative phosphorylation. Cluster analysis of both SLC groups on both diets revealed 5 clusters. One cluster included 396 genes that were salt responsive in NSLC but not HSLC baboons and included protein kinase C, central to calcium‐, PPAR‐, Wnt‐, MAPK‐, and VEGF‐signaling and NADH dehydrogenase, central to oxidative phosphorylation.Conclusions: Baboon kidney showed salt responsiveness in NSLC baboons for signaling pathways central to sensing stress and nutrients; whereas they were down‐regulated or unchanged in HSLC baboons. This suggests that the HSLC blood pressure phenotype is associated with a lack of response to dietary salt for numerous molecular pathways.