Relationship between capillary angiogenesis, fiber type, and fiber size inchronic systemic hypoxia

Whether chronic hypoxia causes angiogenesis in skeletal muscle is controver sial. Male Wistar rats, 5-6 wk of age, were kept at constant 12% O-2 for 3 wk, and frozen sections of their postural soleus (SOL), phasic extensor dig itorum longus (EDL), and tibialis anterior (TA) muscles were compared with those of normoxic controls. Capillary supply increased in SOL muscles [capi llary-to-fiber ratio (C/F) = 2.55 +/- 0.09 hypoxia vs. 2.17 +/- 0.06 normox ia; capillary density (CD) = 942 +/- 14 hypoxia vs. 832 +/- 20 mm(-2) normo xia, P<0.01] but not in EDL muscles (C/F = 1.44 <plus/minus> 0.04 hypoxia v s. 1.42 +/- 0.04 normoxia; CD = 876 +/- 52 hypoxia vs. 896 +/- 24 mm(-2) no rmoxia). The predominantly glycolytic cortex of TA muscles showed higher C/ F after hypoxia (1.79 +/- 0.09 vs. 1.53 +/- 0.05 normoxia, P<0.05), whereas the mainly oxidative TA core with smaller fibers showed no change in capil larity. The region of the SOL muscle with large-sized (mean fiber area 2,84 3 <plus/minus> 128 mum(2)) oxidative fibers (90% type I) had a higher C/F ( by 30%) and CD (by 25%), whereas there was no angiogenesis in the region wi th sparse (76%) and smaller-sized (2,200 +/- 85 mum(2)) type I fibers. Thus systemic hypoxia differentially induces angiogenesis between and within hi ndlimb skeletal muscles, with fiber size contributing either directly (via a metabolic stimulus) or indirectly (via a mechanical stimulus) to the proc ess.