The role of free radicals in the muscle vasodilatation of systemic hypoxia in the rat.
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 O(2) 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 % O(2) for 5 min) was reduced by oxypurinol which inhibits xanthine oxidase (XO): XO generates O(2)(-) from hypoxanthine, a metabolite of adenosine. By contrast, infusion of superoxide dismutase (SOD), which dismutes O(2)(-) to hydrogen peroxide (H(2)O(2)), 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 O(2)(-) and H(2)O(2), 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, O(2)(-) 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 H(2)O(2), which facilitates hypoxia-induced dilatation.
Pyner
Susan
S
Department of Physiology, The Medical School, Vincent Drive, Birmingham B15 2TT, UK.
Coney
Andrew
A
Marshall
Janice M
JM
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism*; D010117:Oxypurinol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D014664:Vasodilation
D005609:Free Radicals; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010117:Oxypurinol; D010100:Oxygen