Relationship between capillary angiogenesis, fiber type, and fiber size in chronic systemic hypoxia

Abstract

Whether chronic hypoxia causes angiogenesis in skeletal muscle is controversial. 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 digitorum longus (EDL), and tibialis anterior (TA) muscles were compared with those of normoxic controls. Capillary supply increased in SOL muscles [capillary-to-fiber ratio (C/F) = 2.55 +/- 0.09 hypoxia vs. 2.17 +/- 0.06 normoxia; capillary density (CD) = 942 +/- 14 hypoxia vs. 832 +/- 20 mm(-2) normoxia, P < 0.01] but not in EDL muscles (C/F = 1.44 +/- 0.04 hypoxia vs. 1.42 +/- 0.04 normoxia; CD = 876 +/- 52 hypoxia vs. 896 +/- 24 mm(-2) normoxia). 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 capillarity. The region of the SOL muscle with large-sized (mean fiber area 2,843 +/- 128 microm(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 with sparse (76%) and smaller-sized (2,200 +/- 85 microm(2)) type I fibers. Thus systemic hypoxia differentially induces angiogenesis between and within hindlimb skeletal muscles, with fiber size contributing either directly (via a metabolic stimulus) or indirectly (via a mechanical stimulus) to the process.