The role of superoxide (O 2 − ) in muscle vasodilation in chronically hypoxic (CH) rats

We have shown in normoxic (N) rats that vasodilation evoked by 5 min acute hypoxia (8%O 2 ) is potentiated by infusion of superoxide dismutase (SOD). We propose O 2 − released during hypoxia is converted to H 2 O 2 by SOD and contributes to muscle vasodilation. CH can induce oxidative stress so we hypothesized this pathway would make a greater contribution. CH male Wistar rats breathed 12%O 2 for 1, 3 and 7 days prior to acute experiments. In anaesthetized N and 1, 3 and 7CH rats femoral vascular conductance was measured 5 min before, during and after 8%O 2 before and after the SOD inhibitor DETC. In N rats DETC had no effect on the response to 8%O 2 but in CH rats, it significantly reduced the response to 8%O 2 with the effect greatest at 1CH. These results suggest that in CH rats a further acute bout of hypoxia evokes the release of O 2 − which contributes to skeletal muscle vasodilation by conversion to vasodilator H 2 O 2 by SOD. Further experiments showed O 2 − release from adenosine via xanthine oxidase does not contribute. Interestingly, the change in contribution of H 2 O 2 to vasodilation evoked by 8%O 2 cannot be explained by a change in SOD activity as hindlimb muscle SOD activity decreased with CH. BHF funded.