Modifications by chronic intermittent hypoxia and drug treatment on skeletal muscle metabolism.
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.
Pastoris
O
O
Institute of Pharmacology, State University of Pavia, Italy.
Dossena
M
M
Foppa
P
P
Arnaboldi
R
R
Gorini
A
A
Villa
R F
RF
Benzi
G
G
D000227:Adenine Nucleotides / Q000378:metabolism; D015765:Almitrine / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D004734:Energy Metabolism / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006146:Guanidines / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010208:Papaverine / Q000494:pharmacology*; D020110:Pinacidil; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D000227:Adenine Nucleotides; D006146:Guanidines; D014665:Vasodilator Agents; D015016:Yohimbine; D020110:Pinacidil; D006003:Glycogen; D015765:Almitrine; D010208:Papaverine