A 31P-NMR study of the acute effects of altered beta-adrenoceptor stimulation on the bioenergetics of skeletal muscle during contraction.

The effects of acute administration of a beta-adrenoceptor agonist (isoprenaline) or antagonist (propranolol) on skeletal muscle contraction and metabolism in the rat have been studied in vivo using 31P-nuclear magnetic resonance spectroscopy and conventional metabolite analysis. In resting muscle, isoprenaline caused a three-fold increase in cyclic AMP concentration, whereas propranolol decreased cyclic AMP concentration by 40%. Isometric contraction of gastrocnemius muscle at a frequency of 4 Hz was caused by supramaximal sciatic nerve stimulation. Altered beta-adrenoceptor stimulation had no effect on contractile performance at any time during the 30 min stimulation period. During the initial stimulation period (0-4 min) intracellular pH decreased to significantly lower values in the isoprenaline-treated animals (6.24 +/- 0.03) compared to either the control (6.44 +/- 0.08) or propranolol-treated (6.42 +/- 0.08) groups. During the subsequent stimulation period (after 15-30 min stimulation at 4 Hz), pH recovered in all experimental groups to values greater than 6.90 and phosphocreatine concentration achieved a constant level at 35-40% of resting values. Calculation of free ADP concentrations using 31P-NMR determined metabolite concentrations and the creatine phosphokinase equilibrium showed that at similar tension development, [ADP]free varied between the three experimental groups; with the lowest (47 +/- 4 microM) and highest (73 +/- 4 microM) values being calculated for the beta-adrenoceptor agonist- and antagonist-treated groups respectively. Upon termination of stimulation, recovery of phosphocreatine concentration to pre-stimulation values was rapid and similar in all experimental groups. However, gastrocnemius muscle ATP concentration, determined by 31P-NMR and analysis of freeze-clamped muscle, was lower in the isoprenaline-treated group. This study has shown that although altered beta-adrenoceptor stimulation had no effect on contractile performance, significant changes in muscle metabolism were observed in vivo; these effects are discussed with respect to the role of beta-adrenoceptors in skeletal muscle.