Recovery of Functional Vasodilation During Skeletal Muscle Regeneration

Abstract

Functional vasodilation underlies the increase in skeletal muscle blood flow to supply the metabolic demands of contracting myofibers. Following injury, myofibers degenerate and then regenerate through satellite cell activation, thereby recapitulating myogenesis. While the microvasculature is also disrupted, the recovery of functional vasodilation during myofiber regeneration is unexplored. The goal of this study was to evaluate the time course and magnitude of the recovery of functional vasodilation in microvascular resistance networks at defined time points during skeletal muscle regeneration (confirmed with histology of muscle cross‐sections). In male C57BL/6J mice (4 months old; n = 5 per group), the gluteus maximus muscle (GM) was injured by local injection of barium chloride solution (1.2% solution, 75 μl). At 5, 10, 21 and 35 days (d) post injury, the resistance network of the GM was evaluated (versus Control) in feed arteries (FA), first‐ (1A), second‐ (2A) and third‐order (3A) arterioles using intravital microscopy in anesthetized mice (pentobarbital sodium; 60 mg/kg). For each branch order, maximal internal diameter (ID; topical sodium nitroprusside, 10−4 M) was not different through 35d (mean values: FA, ~62 μm; 1A, ~55 μm; 2A, ~43 μm; 3A, ~30 μm). Under resting conditions, the ID of all branch orders was greater than Control at 5d and remained elevated in FA at 10d (P<0.05). Respective resting IDs recovered to Control at 21d (FA, ~45 μm; 1A, ~32 μm; 2A, 22 μm; 3A, ~11 μm). Thus, while spontaneous vasomotor tone was initially attenuated throughout the network, it recovered by 21d in all branch orders (FA, ~27%; 1A, ~40%; 2A, ~50%; 3A, 63%). Steady state vasodilation to rhythmic twitch contractions (4 Hz, 30s) was impaired at 5d (with degenerated myofibers), attenuated at 10d (primarily new myofibers), improved through 21d (maturing myofibers) and by 35d was not different from Control. Rapid onset vasodilation to tetanic contraction (100 Hz, 500 ms) was also impaired at 5d, attenuated at 10d (P<0.05), improved through 21d and by 35d was not different from Control across respective branch orders. We suggest that elevated resting diameters with diminished vasomotor tone during the initial stages of regeneration promote tissue perfusion as myofiber recovery begins. During maturation of nascent myofibers, restoration of vasomotor tone underscores the recovery of functional vasodilation to both rhythmic and tetanic contractions. Nevertheless, vasomotor tone recovers sooner than the ability of regenerating myofibers to elicit functional vasodilation.Support or Funding InformationAHA 17PRE33410260, NIH R37 HL041026This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.