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Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism

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Abstract

The energy metabolism was evaluated in gastrocnemius muscle from 3-month-old rats subjected to either mild or severe 4-week intermittent normobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, α-adrenergic (δ-yohimbine), vasodilator (papaverine, pinacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactateto-pyruvate ratio; citrate, α-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Furthermore the Vmax of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The adaptation to chronic intermittent normobaric mild or severe hypoxia induced alterations of the components in the anaerobic glycolytic pathway [as supported by the increased activity of lactate dehydrogenase and/or hexokinase, resulting in the decreased glycolytic substrate concentration consistent with the increased lactate production and lactate-to-pyruvate ratio] and in the mitochondrial mechanism [as supported by the decreased activity of malate dehydrogenase and/or citrate synthase resulting in the decreased concentration of some key components in the tricarboxylic acid cycle]. The effect of the concomitant pharmacological treatment suggests that the action of CNS-acting drugs could be also related to their direct influence on the muscular biochemical mechanisms linked to energy transduction.

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Authors and Affiliations

  1. Istituto di Farmacologia, Università di Pavia, 11, Piazza Botta, I-27100, Pavia, Italia

    O. Pastoris, M. Dossena, P. Foppa, R. Arnaboldi, A. Gorini, R. F. Villa & G. Benzi

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  1. O. Pastoris
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  2. M. Dossena
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  3. P. Foppa
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Pastoris, O., Dossena, M., Foppa, P. et al. Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism. Neurochem Res 20, 143–150 (1995). https://doi.org/10.1007/BF00970538

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