IN-VIVO UNALTERED MUSCLE PROTEIN-SYNTHESIS IN EXPERIMENTAL CHRONIC METABOLIC-ACIDOSIS

In vivo unaltered muscle protein synthesis in experimental chronic met abolic acidosis. Chronic metabolic acidosis (CMA) is a major cause of growth defect, implying disturbances of protein metabolism. Previously in vivo studies performed in the fasting state showed enhanced whole body protein turnover, whereas in vitro studies showed unchanged muscl e protein synthesis. The present study is the first to determine the e ffects of CMA on muscle protein synthesis and degradation in vivo. Two studies were performed in 60 g male rats fed a 30% casein diet. In st udy I, one group was sham-operated (C rats), and two groups underwent subtotal nephrectomy. One of them developed acidosis (UA rats) which w as corrected in the other by NaHCO3 in the diet (UNA rats). Study II c ompared sham-operated rats rendered acidotic by NH4Cl in the drinking water (CA rats) and normal pair-fed (CNA) rats. Fractional protein syn thesis rate (FSR) was determined in gastrocnemius muscle after injecti on of H-3-phenylalanine. Fractional protein degradation rate (FDR) was calculated as FSR minus fractional rate of muscle growth (FGR). In st udy I, UA rats had lower growth and N balance (163 +/- 12 vs. 216 C 11 mg N/day; P < 0.001) than UNA rats, despite identical food intake (11 g/day). This was associated with identical FSR (10.4 +/- 0.5 vs. 10.9 +/- 0.5%/day), but enhanced protein degradation (6.30 +/- 0.99 vs. 5. 10 +/- 0.71%/day; P < 0.05). Plasma insulin, C peptide, PTH and cortic osterone did not differ in UA and UNA rats, whereas plasma IGF-I was m arkedly reduced (147 +/- 21 vs. 283 +/- 27 ng/ml; P < 0.01) in UA rats . C rats fed ad libitum had higher FSR and higher plasma IGF-I (351 +/ - 32 ng/ml), insulin and corticosterone levels than uremic rats, proba bly due to higher food intake (16 g/day). In study II, CA and CNA were pair fed. However, CA rats showed growth defect, and low plasma IGF-I with unchanged FSR (8.3 +/- 0.4 vs. 8.3 +/- 0.3%/day). In conclusion, in uremic as well as in nonuremic rats, muscle protein synthesis meas ured in vivo, in fed awake rats, was not modified by CMA, which increa sed protein degradation possibly through reduced plasma IGF-I.