Hypoxia and pharmacological treatment in differently aged rats: effect on muscular metabolite concentrations

Metabolite concentrations in gastrocnemius and soleus muscles were compared in young-adult (4 months), mature (12 months) and senescent (24 months) rats after continuous (72 consecutive hours) exposure to normobaric hypoxia or normoxia with the intraperitoneal administration of the vasodilator naftidrofuryl or saline solution for 30 days consecutively before hypoxia. The following metabolites were assessed in gastrocnemius muscle in relation to: (a) energy mediators: ATP, ADP, AMP; (b) energy store: creatine phosphate; (c) anaerobic glycolysis: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate; (d) Krebs' cycle: citrate, alpha-ketoglutarate, malate; (e) free amino acids related to Krebs' cycle: aspartate, glutamate, alanine; and (f) ammonia. In the soleus muscle only ATP, creatine phosphate, glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, citrate, alpha-ketoglutarate malate, aspartate and glutamate were assessed. Aging does not seem to affect soleus and gastrocnemius muscles in the same way. Some gastrocnemius muscle metabolites show linear changes in their concentrations with aging, while for the soleus muscle the only linear change relates to glucose 6-phosphate. As regards the influence of hypoxia on muscular metabolism, all the most important changes observed in metabolite concentrations in comparison with control values take place at the age of 4 and 24 months. Furthermore, as regards naftidrofuryl action, the most important variations observed concern only 4-month-old animals. Finally our data show that only in certain cases has pharmacological treatment been able to modify the influence of hypoxic conditions on the concentration of muscle metabolites, regardless of the age of the animals