Differential microvascular response to disuse in rat hindlimb skeletal muscles

The aim of the study was to address discrepant findings in the literature r egarding coupling between decreased functional demand during disuse and red uced capillarity. We previously reported [K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17-32, 1995] that severe disuse of rat exten sor digitorum longus (EDL) muscle caused by a 2-wk application of tetrodoto xin (TTX) on the sciatic nerve is not accompanied by capillary loss. Using the same animal model, the present study examined whether this absence of c oupling could be explained in terms of 1) too short a duration of disuse an d 2) muscle-specific response to disuse. Fischer 344 rats were exposed to e ither no treatment (control) or to 2- or 8-wk. TTX applications. Fiber size , capillary density per fiber cross-sectional area, and capillary-to-fiber (C/F) ratio were determined by morphometry in the EDL muscle (control, 2- a nd 8-wk groups) and in the superficial portion of medial gastrocnemius (Gas ) muscle (control, 2 wk). In both muscles; microvascular blood flow was eva luated by intravital microscopy [red blood cell velocity in capillaries (V- RBC)] and by laser Doppler flowmetry (LDF). Regardless of duration of TTX a pplication or muscle type, TTX-induced disuse resulted in a significant red uction of fiber area (44-71%). However, capillary density increased in EDL muscle both at 2 and 8 wk) but not in Gas muscle. C/F ratio decreased in ED L muscle at 8 wk; (18%) and in Gas muscle (39%). This indicates that the ef fect on capillarity depended on duration of disuse and on muscle type. V-RB C and LDF signal were significantly larger in EDL than in Gas muscle. Analy sis of change in capillarity vs. V-RBC suggested that the outcome of disuse may be modulated by blood flow. We conclude that the duration of skeletal muscle disuse per se does not dictate capillary loss, and we hypothesize th at discrepant findings of coupling between functional demand and capillarit y could be due to the presence/absence of flow-related angiogenesis superim posed on the capillary removal process during disuse.