The effect of isolated chloride depletion on growth and protein turnover in young rats

The effects of feeding a chloride-deficient (CD) diet were examined in young, growing rats. All animals were fed the same sodium-replete, CD diet. The experimental group drank distilled water, while the control group (CS) drank distilled water supplemented with 37 mM sodium chloride. By day 15, the CD rats had negligible concentrations of chloride in their urine and had developed hypochloremic metabolic alkalosis. Both groups had comparable urinary sodium concentrations and creatinine clearances. Food intake (256 vs. 226 g), weight (108.8 vs. 47.0 g) and length (9.6 vs. 7.4 cm) gains were greater in the CS animals and the efficiency of weight gain was lower in the CD rats (25.2 vs. 42.6 g gained/g of food intake). After 15-18 days, blood was drawn for testing, body composition measurements were performed and epitrochlearis muscle protein synthesis and net degradation rates determined. When incubated with or without the addition of insulin (I), epitrochlearis muscle protein synthesis, measured as the incorporation of¹⁴C-phenylalanine, was significantly lower in CD rats [(I+45.7 vs. 36.76) and (I-34.72 vs. 26.3) nmol phenylalanine/g wet weight per hour (both P<0.05)]. Net protein degradation rates were not significantly different between the two groups. Estimated nitrogen balance was significantly diminished in CD compared with CS rats. Gastrocnemius muscle RNA concentrations were also lower in CD rats (1.34 vs. 1.60 mg RNA/g wet weight, P<0.001), but gastrocnemius protein concentrations were equal. These results demonstrate that the growth failure seen in CD rats is associated with diminished nitrogen balance, a decrease in protein synthesis rates and lower muscle RNA concentrations. These findings are also seen in rats with isolated sodium deficiency, and suggest that both sodium and chloride deficiency may act through a common pathway to diminish growth in young animals.