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 they are maintained. We studied acute (6 h) and chronic (1 to 20 d) effects of cimaterol (CIM) on skeletal muscle metabolism and protein accretion by use of close arterial infusion in the hindlimbs of six young steers. Surgical catheterizations were conducted to allow continuous infusion of CIM (.5 microg/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 acids, 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. Cimaterol infusion acutely stimulated blood flow and caused acute mobilization of nitrogen (alanine), NEFA, and lactate from the treated hindlimb. Cimaterol infusion increased net uptake of amino acids (P < .05) in treated and control hindlimbs after 1 d of CIM infusion, but a progressive increase between 1 and 14 d of infusion was observed only in the treated hindlimbs. Net uptake of total amino acids in the treated hindlimb 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 different between treated and control hindlimbs by d 20 of CIM infusion. Integration of net tyrosine and phenylalanine uptake over the entire infusion period predicted a 10% difference in skeletal muscle protein mass between treated and control hindlimbs. Semitendinosus and semimembranosus muscles in the treated hindlimb contained 9 and 11% greater protein content, respectively (P < .05), at the end of the infusion period. 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.