Effects of intra-arterial epinephrine on energy metabolism in exercising rabbit gastrocnemius muscle, studied by in vivo phosphorus nuclear magnetic resonance.
Epinephrine has an inotropic effect on skeletal muscle, especially on glycolytic type 2 fibers. The mechanism of this effect is not completely clear and its association with a change in oxidative metabolism or glycolytic activation was not fully investigated. Epinephrine's effects on muscle bioenergetics were studied by in vivo 31P nuclear magnetic resonance to find if mitochondrial metabolism is changed during the inotropic action and if the known glycolytic activation by epinephrine is operative during muscle twitch. The study was also used as a model for the application of in vivo 31P nuclear magnetic resonance in the evaluation of short-term acting drugs. When injected intra-arterially, epinephrine (1 micrograms/kg) augmented the twitch tension of indirectly stimulated, continuously working rabbit gastrocnemius muscle by 15.4 + 6.5%. This increase in work was associated with reduction of phosphocreatine to inorganic phosphate ratio (PCr/Pi) from 3.4 to 2.1 without change in ATP levels. Intracellular pH was reduced from 6.9 to 6.75, but no accumulation of glycolytic intermediates could be observed. The increase in work was not associated with a rise in ADP. All these changes occurred for a few minutes only. The findings suggest that epinephrine's inotropic action is not mediated by a change in mitochondrial metabolism. Glycolytic activation by epinephrine occurs even during twitch and contributes partly to the energy demands of the augmented force. Epinephrine's inotropic effect is, however, not primarily due to changes in bioenergetic kinetics, but to effects on force generating mechanisms, with secondary reduction in energy state.
Argov
Z
Z
Department of Biochemistry/Biophysics, University of Pennsylvania School of Medicine, Philadelphia.
Nioka
S
S
Eleff
S
S
Chance
B
B
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D007269:Injections, Intra-Arterial; D009682:Magnetic Resonance Spectroscopy; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010758:Phosphorus; D011817:Rabbits
D010758:Phosphorus; D004837:Epinephrine