The role of free radicals in the muscle vasodilatation of systemic hypoxia in the rat

Pyner, S.; Coney, A.M.; Marshall, J.M.

Abstract

Muscle vasodilatation evoked by systemic hypoxia is adenosine mediated and nitric oxide (NO) dependent: recent evidence suggests the increased binding of NO at complex IV of endothelial mitochondria when O2 level falls leads to adenosine release. In this study on anaesthetised rats, the increase in femoral vascular conductance (FVC) evoked by systemic hypoxia (breathing 8% O2 for 5 min) was reduced by oxypurinol which inhibits xanthine oxidase (XO): XO generates O2 from hypoxanthine, a metabolite of adenosine. By contrast, infusion of superoxide dismutase (SOD), which dismutes O2 to hydrogen peroxide (H2O2), potentiated the hypoxia-evoked increase in FVC. However, NO synthesis inhibition reduced the hypoxia-evoked increase in FVC and it was not further altered by SOD. In other studies, the spinotrapezius muscle was pre-loaded with hydroethidine (HE), or dihydrorhodamine (DHR) which fluoresce in the presence of O2 and H2O2, respectively. In muscle loaded with HE, systemic hypoxia increased fluorescence in endothelial cells of arterioles, whereas in muscle loaded with DHR, fluorescence was diffusely located in and around arteriolar endothelium. We propose that in systemic hypoxia, O2 generated by the XO degradation pathway from adenosine released by endothelial cells, and released by endothelial mitochondria by increased binding of NO to complex IV, is dismuted to H2O2, which facilitates hypoxia-induced dilatation.

Citation

Pyner, S., Coney, A., & Marshall, J. (2003). The role of free radicals in the muscle vasodilatation of systemic hypoxia in the rat. Experimental Physiology, 88(6), 733-740. https://doi.org/10.1113/eph8802524

• Journal Article Type: Article
• Publication Date: Nov 1, 2003
• Deposit Date: Jul 3, 2008
• Journal: Experimental Physiology
• Print ISSN: 0958-0670
• Electronic ISSN: 1469-445X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 88
• Issue: 6
• Pages: 733-740
• DOI: https://doi.org/10.1113/eph8802524
• Public URL: https://durham-repository.worktribe.com/output/1558800