Chronic Hypoxia Induces Prolonged Angiogenesis in Skeletal Muscles of Rat

Abstract

Chronic systemic hypoxia results in a series of changes in the respiratory and cardiovascular systems that help preserve tissue oxygenation. In particular, ventilation is increased and erythropoiesis is induced (Ou et al. 1992). Chronic tissue hypoxaemia is thought to provide a stimulus for growth of capillaries (Hudlicka et al. 1992), although whether systemic hypoxia induces angiogenesis in skeletal muscle has been controversial. Thus, chronic hypoxia was shown to increase capillary density, but it was argued that this reflected a decrease in muscle fibre size rather than true angiogenesis (Banchero et al. 1976; Adair et al. 1990). Accordingly, it was reported that exposure to 10 % O 2 for 5 weeks, or 12 % O 2 for 12 weeks did not change capillary to fibre ratio (C:F) in diaphragm or leg muscles of the rat (Snyder et al. 1985; Bigard et al. 1991). By contrast, in a recent study on the rat we showed that chronic systemic hypoxia (at 12 % O 2) for up to 3 weeks did cause angiogenesis, as indicated by an increase in C:F, in diaphragm and soleus muscles, but not in extensor digitorum longus or tibialis anterior muscles (Deveci et al. 2001). We also provided evidence that there was a relationship between fibre size and angiogenesis, such that the increase in C:F was greater in regions of muscle where the fibres were of larger cross-sectional area (Deveci et al. 2001). However, the experiments performed by other groups used a longer period of chronic hypoxia (≥ 6 weeks) than we had used. Given that many adaptations to hypoxia are transient, the aim of the present study was to establish whether 6 weeks of chronic systemic hypoxia induced further angiogenesis between or within muscles. METHODS All experiments were performed in accordance with the UK Animals (Scientific Procedures Act) 1986. Male Wistar rats (5-6 weeks old) were held for 6 weeks in an hypoxic chamber regulated at 12 % O 2 with CO 2 removal (Thomas & Marshall, 1995). Experimental groups were matched for age and mass: initial body mass (BM) was 178 ± 4 g and final BM, 356 ± 7 g (mean ± ..., n = 6); normoxic controls were of similar BM (357 ± 4 g, n = 6). Animals were killed by pentobarbitone overdose

Capillary‐to‐fiber ratio of hind limb muscles in the male Syrian golden hamster

“…Interestingly, the C/F in our hamster soleus muscle was very similar to that found in rat (2.2) (Deveci et al, 2001(Deveci et al, , 2002, despite the fact that rat soleus has a higher percentage of type I fibers than hamster. There are no published values for C/F for rat gastrocnemius, so we are unable to determine if hamster gastrocnemius C/F agrees or disagrees with rat.…”

Chronic hypoxia increases rat diaphragm muscle endurance and sodium-potassium ATPase pump content

“…Chronic hypoxia (CH), a feature of respiratory disease, is known to affect skeletal muscle structure and function. Alterations include changes in capillarity [1,2], fibre size and distribution [3][4][5][6][7][8][9][10], oxidative capacity [5,6,11,12] and contractile performance [5,9,[13][14][15][16]. CH induces reflex hyperventilation.…”

Effects of sustained hypoxia on sternohyoid and diaphragm muscle during development

“…Skeletal muscle has the capacity to adapt to sustained hypoxia by way of modulation of skeletal muscle vasculature [1,2], muscle enzyme activities [3][4][5][6], muscle fibre size and distribution [7][8][9][10] and contractile performance [11][12][13]. Moreover, sustained hypoxia has been shown to elicit functional plasticity in respiratory muscles [9,10] in a manner that differs from the phenotypic changes occurring in limb muscles [10,14,15].…”