Time course of denervation-induced changes in gastrocnemius muscles of adult and old rats.

Denervation leads to significant muscle atrophy, but it is less clear whether 1) loss of capillaries, fibre size and oxidative capacity decline in parallel and 2) the time course of these changes differs between young and old animals. To investigate this, we denervated the left gastrocnemius muscle for 1, 2 or 4 weeks, while the right muscle served as an internal control, in rats that were 5 or 25 months old at the end of the experiment. In the fast part of the gastrocnemius muscle, almost all atrophy had occurred after two weeks (42%) of denervation. Even after 4 weeks of denervation, there was no significant reduction in the oxidative capacity of the muscle. Significant capillary loss occurred only after 4 weeks of denervation (P < 0.001) that lagged behind and was less than proportional to the decrease in fibre size. Consequently, the capillary density was elevated (P < 0.001). The time course of these morphological changes was similar in the 5- and 25-month-old rats. Comparing these data with those previously published in the soleus muscle from the same animals show that the decrease in oxidative capacity and capillary rarefaction were more pronounced and occurred earlier than in the gastrocnemius muscle, respectively. The time course of capillary loss lagged behind the decrease in fibre size, and combined with the absence of denervation-induced changes in oxidative capacity this resulted in a muscle capillary supply in excess of that expected by the metabolism and fibre size at least during the first 4 weeks after denervation.