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

Abstract

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 H 2 O 2 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 weeks old rats had decreased Na + ,K + -ATPase activity when compared to 13 and 52 weeks old rats. In renal medulla, 91 weeks old rats had increased Na + ,K + -ATPase activity, paralleled by an increase in protein expression of α 1 -subunit of Na + ,K + -ATPase. In addition, renal H 2 O 2 production increased with age and at 91 weeks of age renal medulla H 2 O 2 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.

Renal Redox Balance and Na+, K+-ATPase Regulation: Role in Physiology and Pathophysiology

“…Furthermore, not only was Na + ,K + -ATPase activity increased in renal medulla of aged Wistar Kyoto rats but also, in this part of the kidney, hydrogen peroxide production was increased with age and in comparison with renal cortex (Silva et al, 2010). Given that Na + ,K + -ATPase regulation differs between the proximal and distal nephron segments it is possible that, in the renal medulla, increased reactive oxygen species may activate cell specific signal pathways that up-regulate Na + ,K + -ATPase activity.…”

“…In the renal medulla where the final regulation of sodium and potassium in the urine takes place, ageing was accompanied by a significant increase in Na + ,K + -ATPase activity and expression of the 1 -subunit (Silva et al, 2010). Furthermore, not only was Na + ,K + -ATPase activity increased in renal medulla of aged Wistar Kyoto rats but also, in this part of the kidney, hydrogen peroxide production was increased with age and in comparison with renal cortex (Silva et al, 2010).…”

“…In the proximal tubules of aged rats age-related increase in reactive oxygen species levels were found to be responsible for decreased basal Na + ,K + -ATPase activity (Asghar et al, 2001;Silva et al, 2010). The molecular mechanism responsible for the observed decrease in Na + ,K + -ATPase activity was a higher basal Na + ,K + -ATPase phosphorylation due to reactive oxygen species-mediated increase in protein kinase C activity (Asghar et al, 2003;Asghar et al, 2001;Asghar & Lokhandwala, 2004) (Figure 6).…”

“…Given the key role of Na + ,K + -ATPase for normal renal function changes in Na + ,K + -ATPase regulation are associated with the development of several conditions such as hypertension, obesity-associated hypertension and diabetes as well as during the ageing process (Jaitovich et al, 2010;Silva et al, 2010;Vague et al, 2004;Wang et al, 2009). As such understanding the mechanisms involved in regulation of Na + ,K + -ATPase throughout the nephron is of major importance.…”

Age-related changes in renal AQP3 and AQP4 expression in Sprague Dawley rats

“…Decreased renal function and increased susceptibility to chronic kidney diseases are observed in aging kidneys, primarily due to glomerulosclerosis, tubular atrophy, interstitial fibrosis, and loss of functional renal mass (Martin and Sheaff, 2007;Silva et al, 2010) Aquaporins (AQPs) are a family of small membrane proteins of approximately 30 kDa that serve as semi-permeable channels. AQPs are also called major intrinsic proteins, which facilitate water transport across biological membranes (Xing et al, 2014), and are involved in diverse physiological functions including brain water balance, cell migration, cell proliferation, neuro-excitation, fat metabolism, and epidermal hydration (Tradtrantip et al, 2009).…”