THE BETA-AGONIST CIMATEROL DIRECTLY ENHANCES CHRONIC PROTEIN ACCRETION IN SKELETAL-MUSCLE

Our objective was to determine whether the chronic anabolic effects of beta-adrenergic agonists on skeletal muscle are direct and how long t hey are maintained. We studied acute (6 h) and chronic (1 to 20 d) eff ects of cimaterol (CIM) on skeletal muscle metabolism and protein accr etion by use of close arterial infusion in the hindlimbs of six young steers. Surgical catheterizations were conducted to allow continuous i nfusion of CIM (.5 mu g/min) or saline into the external iliac artery of contralateral hindlimbs and simultaneous sampling for arteriovenous difference measurements. Hindlimb blood flow and net flux of amino ac ids, glucose, lactate, and NEFA were determined during a basal period before infusion, at 6 h, and at 1, 3, 7, 14, and 20 d of infusion. Cim aterol infusion acutely stimulated blood flow and caused acute mobiliz ation of nitrogen (alanine), NEFA, and lactate from the treated hindli mb. Cimaterol infusion increased net uptake of amino acids (P < .05) i n treated and control hindlimbs after 1 d of CIM infusion, but a progr essive increase between I and 14 d of infusion was observed only in th e treated hindlimbs. Net uptake of total amino acids in the treated hi ndlimb was increased 50 and 80% (P < .05) at 7 and 14 d, respectively, when compared to the control hindlimb and was increased 260% at d 14 when compared with the basal period. Net amino acid uptake was not dif ferent between treated and control hindlimbs by d 20 of CIM infusion. Integration of net tyrosine and phenylalanine uptake over the entire i nfusion period predicted a 10% difference in skeletal muscle protein m ass between treated and control hindlimbs. Semitendinosus and semimemb ranosus muscles in the treated hindlimb contained 9 and 11% greater pr otein content, respectively(P < .05), at the end of the infusion perio d. Results provide a quantitative description of the temporal pattern of transient effects of CIM on skeletal muscle metabolism and protein accretion and provide evidence that these are direct effects.