Renal aging in WKY rats: Changes in Na+,K+-ATPase function and oxidative stress

It has been suggested that alterations in Na+,K+-ATPase mediate the development of several aging-related pathologies, such as hypertension and diabetes. Thus, we evaluated Na+,K+-ATPase function and H2O2 production in the renal cortex and medulla of Wistar Kyoto (WKY) rats at 13, 52 and 91 weeks of age. Creatinine clearance, proteinuria, urinary excretion of Na+ and K+ and fractional excretion of Na+ were also determined.The results show that at 91 weeks old WKY rats had increased creatinine clearance and did not have proteinuria. Despite aging having had no effect on urinary Na+ excretion, urinary K+ excretion was increased and fractional Na+ excretion was decreased with age. In renal proximal tubules and isolated renal cortical cells, 91 week old rats had decreased Na+,K+-ATPase activity when compared to 13 and 52 week old rats. In renal medulla, 91 week old rats had increased Na+,K+-ATPase activity, paralleled by an increase in protein expression of α1-subunit of Na+,K+-ATPase. In addition, renal H2O2 production increased with age and at 91 weeks of age renal medulla H2O2 production was significantly higher than renal cortex production.The present work demonstrates that although at 91 weeks of age WKY rats were able to maintain Na+ homeostasis, aging was accompanied by alterations in renal Na+,K+-ATPase function. The observed increase in oxidative stress may account, in part, for the observed changes. Possibly, altered Na+,K+-ATPase renal function may precede the development of age-related pathologies and loss of renal function.

Research Highlights
► Aging is accompanied by diminished capacity of proximal tubule Na+ reabsorption.
► Na+,K+-ATPase activity decreases in renal proximal tubules and increases in renal medulla.
► Aged rats have changes in redox homeostasis with a pronounced increase in renal medulla production of H2O2.