Regulation of gene expression in renal papilla and cardiac ventricle in response to dietary Na + restriction

The kidneys and cardiovascular system maintain volume homeostasis and blood pressure by responding to reduction in dietary Na + intake. We examined Na + -dependent changes in gene expression in the renal papilla and heart ventricle of rats. Animals were conditioned with control or low-Na + diets for 1 week. RNA isolated from kidneys or hearts was analyzed by RNAseq. In the renal papilla, notable genes upregulated in response to low dietary Na + included α, β and γ subunits of ENaC, α and β subunits of the Na/K-ATPase, and the transcription factor Zbtb16. Increases in mRNA for the ENaC were confirmed using qPCR and were strongly dependent on location within the kidney with papilla > outer medulla > cortex. Differences in ENaC protein expression exhibited a similar dependence on location. The effects of dietary Na + on ENaC expression, as well as that of Zbtb16, in the papillae were not mimicked by treatment with aldosterone, indicating that other factors contribute to the adaptation to Na + deprivation. In the heart, a smaller number of genes were affected by dietary Na + . Effects included downregulation of transcripts for the natriuretic peptides ANP and BNP and of Acta1. Enrichment analyses indicated that low dietary Na + led to upregulation of many Gene Ontology (GO) gene sets related to growth and development in the kidney samples, but downregulation of such gene sets in the heart. Our results illustrate the profound site- and tissue-specific effects of changes in dietary Na + on renal and cardiac gene expression and regulation of salt balance.