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

Neurochem Res. 1995 Feb;20(2):143-50. 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.

Publication types

  • Comparative Study

MeSH terms

  • Adenine Nucleotides / metabolism
  • Almitrine / pharmacology*
  • Animals
  • Chronic Disease
  • Energy Metabolism* / drug effects
  • 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
  • Time Factors
  • Vasodilator Agents / pharmacology
  • Yohimbine / pharmacology*


  • Adenine Nucleotides
  • Guanidines
  • Vasodilator Agents
  • Yohimbine
  • Pinacidil
  • Glycogen
  • Almitrine
  • Papaverine