In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis

In vivo unaltered muscle protein synthesis in experimental chronic metabolic 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 muscle protein synthesis. The present study is the first to determine the effects of CMA on muscle protein synthesis and degradation in vivo. Two studies were performed in 60g male rats fed a 30% casein diet. In study I, one group was sham-operated (C rats), and two groups underwent subtotal nephrectomy. One of them developed acidosis (UA rats) which was corrected in the other by NaHCO3 in the diet (UNA rats). Study II compared sham-operated rats rendered acidotic by NH4Cl in the drinking water (CA rats) and normal pair-fed (CNA) rats. Fractional protein synthesis rate (FSR) was determined in gastrocnemius muscle after injection of 3H-phenylalanine. Fractional protein degradation rate (FDR) was calculated as FSR minus fractional rate of muscle growth (FGR). In study I, UA rats had lower growth and N balance (163 ± 12 vs. 216 ± 11mg 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 corticosterone did not differ in UA and UNA rats, whereas plasma IGF-I was markedly 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, probably 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 measured in vivo, in fed awake rats, was not modified by CMA, which increased protein degradation possibly through reduced plasma IGF-I.