MODIFICATIONS BY CHRONIC INTERMITTENT HYPOXIA AND DRUG-TREATMENT ON SKELETAL-MUSCLE METABOLISM

The energy metabolism was evaluated in gastrocnemius muscle from 3-mon th-old rats subjected to either mild or severe 4-week intermittent nor mobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, alpha-adrenergic (delta-yohimbine), vasodilator (papaverine, p inacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: gly cogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyr uvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartat e, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Fur thermore the Vmax of the following muscular enzymes was evaluated: hex okinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reduct ase; cytochrome oxidase. The adaptation to chronic intermittent normob aric mild or severe hypoxia induced alterations of the components in t he anaerobic glycolytic pathway [as supported by the increased activit y of lactate dehydrogenase and/or hexokinase, resulting in the decreas ed glycolytic substrate concentration consistent with the increased la ctate production and lactate-to-pyruvate ratio] and in the mitochondri al mechanism [as supported by the decreased activity of malate dehydro genase and/or citrate synthase resulting in the decreased concentratio n 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.