Recovery of blood flow regulation in microvascular resistance networks during regeneration of mouse gluteus maximus muscle.

Myofibre regeneration after skeletal muscle injury is well-studied, although little is known about how microvascular perfusion is restored. The present study aimed to evaluate the recovery of blood flow regulation during skeletal muscle regeneration. In anaesthetized male C57BL/6J mice (aged 4 months), the gluteus maximus muscle (GM) was injured by local injection of barium chloride solution (1.2%, 75 μL). Functional integrity of the resistance network was evaluated at 5, 10, 21 and 35 days post-injury vs. Control by measuring internal diameter of feed arteries, first-, second- and third-order arterioles supplying the GM using intravital microscopy. The resting diameters of all branch orders were significantly greater (P < 0.05) than Control at 5 and 10 days and recovered to Control by 21 days, as did spontaneous vasomotor tone. Vasodilatation to ACh and vasoconstriction to phenylephrine (10-9 to 10-5  m) were absent at 5 days, increased at 10 days and recovered to Control by 21 days; reactivity improved in a distal-to-proximal gradient. Across branch orders, functional vasodilatation to single tetanic contraction (100 Hz, 500 ms) and to rhythmic twitch contractions (4 Hz, 30 s) was impaired at 5 days, improved through 21 days and was not different from Control at 35 days. Peak force development (g) was 60% of Control at 10 days and recovered by 21 days. Diminished vasomotor tone during the initial stages of regeneration promotes tissue perfusion as myofibre recovery begins. Recovery of tone and vasomotor responses to agonists occur in concert with myofibre regeneration. Delayed recovery of functional vasodilatation indicates that additional time is required to restore signalling between contracting myofibres and their vascular supply.