Acute metabolic acidosis inhibits muscle protein synthesis in rats

Department of Surgery, State University of New York at Stony Brook, Stony Brook, New York 11794 Submitted 26 August 2003 ; accepted in final form 18 February 2004 In this study, we investigated the effect of acute metabolic acidosis on tissue protein synthesis. Groups of rats were made acidotic with intragastric administration of NH 4 Cl (20 mmol/kg body wt every 12 h for 24 h) or given equimolar amounts of NaCl (controls). Protein synthesis in skeletal muscle and a variety of different tissues, including lymphocytes, was measured after 24 h by injection of L -[ 2 H 5 ]phenylalanine (150 µmol/100 g body wt, 40 moles percent). Results show that acute acidosis inhibits protein synthesis in skeletal muscle (–29% in gastrocnemius, –23% in plantaris, and –17% in soleus muscles, P < 0.01) but does not affect protein synthesis in heart, liver, gut, kidney, and spleen. Protein synthesis in lymphocytes is also reduced by acidosis (–8%, P < 0.05). In a separate experiment, protein synthesis was also measured in acidotic and control rats by a constant infusion of L -[ 2 H 5 ]phenylalanine (1 µmol·100 g body wt –1 ·h –1 ). The results confirm the earlier findings showing an inhibition of protein synthesis in gastrocnemius (–28%, P < 0.01) and plantaris (–19%, P < 0.01) muscles but no effect on heart and liver by acidosis. Similar results were also observed using a different model of acute metabolic acidosis, in which rats were given a cation exchange resin in the H + (acidotic) or the Na + (controls) form. In conclusion, this study demonstrates that acute metabolic acidosis for 24 h depresses protein synthesis in skeletal muscle and lymphocytes but does not alter protein synthesis in visceral tissues. Inhibition of muscle protein synthesis might be another mechanism contributing to the loss of muscle tissue observed in acidosis. L -[ 2 H 5 ]phenylalanine; flooding method; constant infusion; ammonium chloride; lymphocytes Address for reprint requests and other correspondence: G. Caso, Dept. of Surgery, HSC T19-048, State Univ. of New York at Stony Brook, Stony Brook, NY 11794-8191 (E-mail: Giuseppe.Caso{at}stonybrook.edu ).