Microvascular response to ischemia, and endothelial ultrastructure, in disused skeletal muscle

It has previously been demonstrated that muscle atrophy associated with aging and disuse is accompanied by changes in microvascular function including absolute loss of capillaries, increased mean red blood cell velocity (VRBC), and absence of reactive hyperemia. The purpose of the present study was to determine whether disuse could account for these changes. The right extensor digitorum longus muscle in male Fisher 344 rats was subjected to 15 days of disuse through the neural application of tetrodotoxin (TTX). Microvascular function, as assessed using intravital microscopy, was compared for muscles from control (n = 8) and TTX-treated (n = 5) animals. The TTX-induced disuse was associated with a 40.5% decrease in muscle weight, a 51.6% decrease in fiber cross-sectional area, a 62% decrease in mitochondrial volume density, and increased capillary damage (TTX, 11% control, 1.1%). Although capillary density in the disused muscle increased (by 139%), when corrected for muscle atrophy, the absolute number of capillaries was maintained. With TTX disuse, VRBC heterogeneity was not different from that in the control rats while the mean velocity increased 3.18x. TTX disuse did not alter the pattern of reactive hyperemia following 30 min of complete ischemia. These results suggest that short-term TTX-induced atrophy affects both microvascular structure and resting state blood flow in rat skeletal muscle, but it does not affect the vascular responsiveness following a metabolic challenge.