Age-related changes in renal function, membrane protein metabolism, and Na,K-ATPase activity and abundance in hypokalemic F344 x BNF(1) rats.
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.
Eiam-Ong
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Department of Internal Medicine, The Combined Program in Nephrology and Renal Physiology, Texas Tech University Health Sciences Center, Lubbock, Tex. 79430, USA.
Sabatini
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D000367:Age Factors; D000375:Aging; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D004032:Diet; D004591:Electrophoresis, Polyacrylamide Gel; D007008:Hypokalemia / Q000097:blood / Q000503:physiopathology*; D015151:Immunoblotting; D007668:Kidney / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D011188:Potassium / Q000008:administration & dosage / Q000097:blood; D011191:Potassium Deficiency / Q000097:blood; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D008565:Membrane Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium