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

• Published in: Neurochemical research Vol. 20; no. 2; pp. 143 - 150
• Main Authors: PASTORIS, O, DOSSENA, M, FOPPA, P, ARNABOLDI, R, GORINI, A, VILLA, R. F, BENZI, G
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-02-1995
• Subjects: Adenine Nucleotides - metabolism; Almitrine - pharmacology; Animals; Biological and medical sciences; Chronic Disease; Energy Metabolism - drug effects; Fundamental and applied biological sciences. Psychology; Glycogen - metabolism; Glycolysis; Guanidines - pharmacology; Hypoxia - metabolism; Male; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - enzymology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Papaverine - pharmacology; Pinacidil; Rats; Rats, Wistar; Stereoisomerism; Striated muscle. Tendons; Time Factors; Vasodilator Agents - pharmacology; Vertebrates: osteoarticular system, musculoskeletal system; Yohimbine - pharmacology; Oxygen; Vertebrata; Energy metabolism; Mammalia; Rat; Rodentia; Environmental factor; Hypoxia; Gastrocnemius muscle; Striated muscle
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/BF00970538

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, alpha-adrenergic (delta-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, lactate-to-pyruvate ratio; citrate, alpha-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.