The effect of cold and hypoxia on angiogenesis in oxidative and glycolytic muscle of rats

Abstract

The angiogenic response of glycolytic (tibialis anterior, TA) and oxidative (soleus, SOL) muscles of rats to progressive cooling (20 to 5degreesC) for 4 weeks and hypoxia (12%O-2) for 3 weeks was investigated. Consistent areas were investigated in each muscle, with the TA divided into core and cortex regions. Cold exposure increased capillary-to-fibre ratio (C/F) in SOL from 1.97 +/- 0.06 to 2.37 +/- 0.17 (P<0.05, ANOVA), but not in the TA. Capillary density (CD, mm(-2)) and fibre cross sectional area (FCSA, mum(-2)) did not change in either muscle. However, proliferating cell nuclear antigen (PCNA) density increased in SOL (52. +/- 9 vs. 88 +/- 8 mm(-1), P<0.05) and staining co-localised with capillaries also increased from 5.1 +/- 1.6 to 12.9 +/- 1.1 mm-2 (P<0.05) in cold acclimated rats. Hypoxia-induced angiogenesis also occurred in SOL (C/F 2.19 +/- 0.10 vs. 2.64 +/- 0.15, P<0.05), but not in the TA when averaged across the whole muscle. However, in the cortex region of TA angiogenesis was seen (1.45 +/- 0.02 vs. 1.83 +/- 0.07) where FCSA was largest. PCNA density increased in SOL and that co-localised with capillaries also increased in hypoxic rats. These results show that both cold acclimation and hypoxia stimulate angiogenesis in SOL. This may indicate that oxidative capacity and muscle activity levels are important factors for angiogenesis.