Age-Related Changes in Renal Function, Membrane Protein Metabolism, and Na,K-ATPase Activity and Abundance in Hypokalemic F344 × BNF&lt;sub&gt;1&lt;/sub&gt; Rats

Eiam-Ong, Somchit; Sabatini, Sandra

doi:10.1159/000022098

Cited by 18 publications

(6 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study demonstrates an age‐related fall in plasma aldosterone level, from 23.6 to 13.2 ng/dL. A similar fall in plasma aldosterone in aging rats was reported by Eiam‐Ong and Sabatini (), but not by Tian et al. ().…”

Section: Discussionsupporting

confidence: 92%

Sodium-pump gene-expression, protein abundance and enzyme activity in isolated nephron segments of the aging rat kidney

et al. 2015

View full text Add to dashboard Cite

Aging is associated with alteration in renal tubular functions, including sodium handling and concentrating ability. Na-K-ATPase plays a key role in driving tubular transport, and we hypothesized that decreased concentrating ability of the aging kidney is due in part to downregulation of Na-K-ATPase. In this study, we evaluated Na and K balance, aldosterone levels, and Na-K-ATPase gene expression, protein abundance, and activity in aging rat kidney. Na-K-ATPase activity (assayed microfluorometrically), mRNA (RT-PCR), and protein abundance (immunoblotting) were quantitated in the following isolated nephron segments: PCT, PST, MTAL, DCT, and CCD from 2, 8, 15, and 24 month-old-rats. In the course of aging, creatinine clearance decreased from 0.48 ± 0.02 mL/min/100 g BW to 0.28 ± 0.06 (P < 0.001) and aldosterone decreased from 23.6 ± 0.8 ng/dL to 13.2 ± 0.6 (P < 0.001). Serum Na+ and K+ increased by 4.0% and 22.5%, respectively. Na-K-ATPase activity, mRNA, and protein abundance of the α1 subunit displayed similar trends in all assayed segments; increasing in PCT and PST; decreasing in MTAL and DCT; increasing in CCD: in PCT they increased by 40%, 75%, and 250%, respectively; while in PST they increased by 80%, 50%, and 100%, respectively (P < 0.001). In MTAL they declined by 36%, 24%, and 34%, respectively, and in DCT by 38%, 59%, and 60%, respectively (P < 0.001). They were higher in CCD by 110%, 115%, and 246%, respectively (P < 0.001). Rats maintained Na/K balance; however with a steady state elevated serum K+. These results reveal quantitative changes in axial distribution of Na-K-ATPase at the level of gene expression, protein abundance, and activity in the nephrons of aging animals and may explain, in part, the pathophysiology of the senescent kidney.

show abstract

Section: Discussionsupporting

confidence: 92%

Sodium-pump gene-expression, protein abundance and enzyme activity in isolated nephron segments of the aging rat kidney

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Compared to younger participants, the BP of elderly patient is more sensitive to salt intake [ 17 , 18 ]. The ability of sodium excretion is reduced in the elderly because of a multitude of factors including a decrease in renal function, reduced synthesis of natriuretic substances, and reduced activity of membrane sodium/potassium-adenosine triphosphatase [ 17 , 24 , 25 ]. Salt taste acuity also reduces with advancing age, and increased sodium intake is observed in middle and old ages [ 13 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Associations of sodium intake with obesity, metabolic disorder, and albuminuria according to age

Koo

Han

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

Sodium intake is associated with obesity and metabolic disorder in the general population. However, sodium intake is significantly reduced according to the decrease of energy intake in older adults although the prevalence of obesity is higher than younger adults. We evaluate the association of sodium excretion (UNa) with blood pressure, obesity, metabolic disorders, and albuminuria according to age. An observational study using data from the Korean National Health and Nutrition Examination Survey IV-V (2008–2011) was performed (N = 18,146). The 24 hour UNa was estimated from a single fasting urine sample.Participants aged≥75 years showed the highest risk for hypertension (HTN) in the highest quartile of UNa (1.769, 95% CI, 1.174–2.665), and the risks for HTN increased with advancing age. Obesity was not associated with UNa in participants aged≥75 years, and hypertriglyceridemia and body fat were not related to UNa in participants aged≥65 years, although these values were significantly associated with UNa in participants aged<65 years. Impaired fasting glucose (IFG) and insulin resistance (IR) were associated with UNa only in participants aged 20–39 years. The highest quartile of UNa showed a 3.777 fold increased risk for albuminuria in those aged 20–39 years (95% CI, 1.130–12.630), and a 1.885 fold increased risk (95% CI, 1.156–3.075) among participants aged 40–64 years. In participants aged≥65 years, albuminuria was not associated with UNa. In contrast with HTN, UNa was not associated with albuminuria, obesity, hypertriglyceridemia, IFG, and IR in older adults despite a strong association in younger adults.

show abstract

“…29,30 The Fischer 344 X Brown Norway rat expresses greater longevity than Fischer 344 animals with rescue from many of their age-related deficits, including the decline in renal function. 31,32 In an attempt to rule out elevated SBP during aging as a contributor to activation of the intrarenal RAS, we studied male Fischer 344 rats between 3 and 15 months of age 33 ( Figure 3A). As expected, SBP did not increase and is actually lower in older than in younger rats.…”

Section: Intrarenal Ras Regulation In Animals Without Age-related Hypmentioning

confidence: 99%

Lewis K. Dahl Memorial Lecture

Diz

2008

Hypertension

View full text Add to dashboard Cite

identified many of the relationships that underlie our current thinking and focus of research on hypertension. Among the first to establish the interactions between salt and hypertension, the realization that genetic factors played a major role in how the kidney responded to salt loads 1 led to development of the genetically predisposed Dahl salt-sensitive rat. His research, although not specifically directed toward aging, recognized that the effects of high-salt diets were not necessarily immediate. In fact, he suggested that at least one third of the life span was required for salt-induced changes in systolic blood pressure (SBP).I am very grateful for the honor of presenting the Dahl lectureship on work, which, over the past several years, has had aging as the focus. The emphasis has been on the autonomic nervous system, as influenced by the renin-angiotensin system (RAS), specifically, the balance between angiotensin (Ang) II and Ang-(1-7) and the contributions of brain cardiovascular areas to the constellation of changes occurring with advancing age. The overall message derived is that, although the brain RAS plays a major role in all of the age-related changes in cardiovascular and metabolic function, neither the SBP nor the metabolic changes appear to be initiating factors in the activation of the intrarenal RAS or the decline in kidney function during aging ( Figure 1). Differential Regulation of the Circulating and Intrarenal RAS During AgingComponents of the classical circulating RAS, in particular, renin release from the juxtaglomerular cells of the kidney, undergo a decline in older animals. This includes reductions in renal tissue renin mRNA, juxtaglomerular cell renin content, responsiveness of renin release to various challenges, and plasma renin and angiotensin (Ang) II. [2][3][4][5][6][7][8][9] The renal vasoconstrictor responses to exogenously administered Ang II are increased in older animals, 6 perhaps resulting from the reductions in the circulating system. In striking contrast, however, kidney Ang II content increases in older animals. 6This latter finding is not surprising, because all of the components of the RAS are synthesized locally within the kidney, 10 -12 and local production of Ang peptides is regulated independent of the circulating system. 11,13-16 Thus, whereas the juxtaglomerular cell renin and its release into the circulation are considered representative of the circulating/hormonal RAS, renal tissue content, tubular fluid, or urinary RAS components are considered representative of the intrarenal RAS.The concept of differential regulation of the circulating and intrarenal or other tissue RAS is not new.12 One possibility for these differences relate to the increase in SBP. An increase in arterial pressure during aging may lead to a baromediated reduction in renin release from the kidney, contributing to the decline in the circulating RAS. In contrast, for the intrarenal system, there is evidence that the regulation of tubular renin may be opposite to or at least different fro...

show abstract

Age-Related Changes in Renal Function, Membrane Protein Metabolism, and Na,K-ATPase Activity and Abundance in Hypokalemic F344 × BNF<sub>1</sub> Rats

Cited by 18 publications

References 40 publications

Sodium-pump gene-expression, protein abundance and enzyme activity in isolated nephron segments of the aging rat kidney

Sodium-pump gene-expression, protein abundance and enzyme activity in isolated nephron segments of the aging rat kidney

Associations of sodium intake with obesity, metabolic disorder, and albuminuria according to age

Lewis K. Dahl Memorial Lecture

Contact Info

Product

Resources

About