Age-related changes in renal function, membrane protein metabolism, and Na,K-ATPase activity and abundance in hypokalemic F344 x BNF(1) rats.

Abstract

BACKGROUND:

Potassium depletion is a common electrolyte abnormality in elderly humans, usually as a consequence of diuretic use or poor oral intake. Hypokalemia is associated with a number of changes in renal function and an increase in some renal membrane transporters; its growth-promoting effect in young animals is well known. With aging, the renal adaptation to a number of challenges is often diminished. We hypothesized that aging is related to decreases in renal function, renal membrane protein metabolism, as well as Na, K-ATPase protein abundance and activity in both control animals as well as in those with potassium depletion.

OBJECTIVE:

We examined the effects of dietary-induced hypokalemia in true-aged nonobese rats (30 months old) on renal function, cortical brush border membrane (BBM) and basolateral membrane (BLM) protein metabolism, and Na,K-ATPase protein abundance and activity. We compared the results obtained to those seen in their 4-month-old counterparts similarly treated.

METHODS:

Young (4-month-old) and senescent (30-month-old) male Fisher 344 x Brown-Norway F(1) rats (F344 x BNF(1)) were fed either a normal or potassium-deficient diet for 7 days. At 24 h, the U-(14)C-leucine incorporation was measured for determination of protein metabolism in renal BBM and BLM. Cortical BLM vesicle and microdissected proximal convoluted tubule (PCT) Na, K-ATPase activities were determined along with Western blot analysis of the cortical BLM alpha(1) subunit of Na,K-ATPase. Metabolic and renal function parameters were also examined.

RESULTS:

Hypokalemia caused hyperbicarbonatemia, hyperglycemia, and azotemia, but only in the senescent animals. The aged control rats had a higher basal level of urine volume, ammonium excretion, and fractional excretion of chloride. By contrast, aging in the F344 x BNF(1) rats was associated with a decrease in plasma aldosterone (by 35%) and phosphate (by 40%) levels as compared with their young controls. Hypokalemia resulted in a significant reduction of plasma aldosterone and a rise in muscle sodium concentration in both age groups; it significantly increased renal BBM and BLM protein concentrations in the young group, while these parameters remained unchanged in the senescent rats. The aged potassium-depleted animals showed a 14% decrease in BBM protein biosynthesis, but there were no changes in the young hypokalemic rats. Both potassium-depleted elderly and young rats had a significant reduction (by 33%) in BLM protein biosynthesis. Hypokalemia significantly increased the Na, K-ATPase activity in both cortical BLM vesicles and in microdissected PCT. The percentage increase in microdissected PCT segments (Na,K-ATPase activity) in elderly potassium-depleted animals was significantly less than that seen in hypokalemic young ones. Aging, per se, was associated with decreased basal microdissected PCT Na,K-ATPase activity in control animals. Hypokalemia had no effect on cortical BLM alpha(1) subunit Na, K-ATPase protein abundance in either age group.

CONCLUSIONS:

The present study provides the first evidence in nonobese aged rats as to the metabolic parameters, renal function, renal cortical membrane protein metabolism, and transporter Na,K-ATPase activity and abundance during potassium depletion. The aged nonobese F344 x BNF(1) rats responded differently from their young nonobese counterparts following potassium depletion. These differences may contribute substantially to the effects often encountered in elderly humans receiving diuretics or having a poor dietary potassium intake.

• Authors: S Eiam-Ong, S Sabatini
• Journal: Gerontology (Gerontology) 1999 Sep-Oct Vol. 45 Issue 5 Pg. 254-64 ISSN: 0304-324X [Print] Switzerland
• PMID: 10460986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Membrane Proteins
• Sodium-Potassium-Exchanging ATPase
• Potassium

Topics

• Age Factors
• Aging
• Animals
• Cell Membrane (enzymology, metabolism)
• Diet
• Electrophoresis, Polyacrylamide Gel
• Hypokalemia (blood, physiopathology)
• Immunoblotting
• Kidney (physiology)
• Kidney Tubules, Proximal (enzymology)
• Male
• Membrane Proteins (metabolism)
• Microvilli (metabolism)
• Potassium (administration & dosage, blood)
• Potassium Deficiency (blood)
• Rats
• Rats, Inbred BN
• Rats, Inbred F344
• Sodium-Potassium-Exchanging ATPase (metabolism)