title: Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis.
abstract: Chronic renal failure (CRF) is associated with metabolic acidosis and abnormal muscle protein metabolism. As we have shown that acidosis by itself stimulates muscle protein degradation by a glucocorticoid-dependent mechanism, we assessed the contribution of acidosis to changes in muscle protein turnover in CRF. A stable model of uremia was achieved in partially nephrectomized rats (plasma urea nitrogen, 100-120 mg/dl, blood bicarbonate less than 21 meq/liter). CRF rats excreted 22% more nitrogen than pair-fed controls (P less than 0.005), so muscle protein synthesis and degradation were measured in perfused hindquarters. CRF rats had a 90% increase in net protein degradation (P less than 0.001); this was corrected by dietary bicarbonate. Correction of acidosis did not reduce the elevated corticosterone excretion rate of CRF rats, nor did it improve a second defect in muscle protein turnover, a 34% lower rate of insulin-stimulated protein synthesis. Thus, abnormal nitrogen production in CRF is due to accelerated muscle proteolysis caused by acidosis and an acidosis-independent inhibition of insulin-stimulated muscle protein synthesis.
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D007328:Insulin / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000378:metabolism*
chemical_list: D007328:Insulin; D009124:Muscle Proteins