High oxygen tension constricts epineurial arterioles of the rat sciatic nerve via reactive oxygen species

Microcirculation of the sheath of the rat sciatic nerve fiber was investigated by using an intravital microscope, and changes in the diameter of the epineurial arterioles in response to highly oxygenated Krebs-bicarbonate solution were evaluated. Superfusion of low-oxygen (0%) Krebs-bicarbonate solution (LKS) onto rat sciatic nerves did not affect changes in the diameter of the arterioles. Nifedipine, a Ca(2+)-channel blocker, caused a dose-dependent dilation of the epineurial arterioles in LKS. In contrast, superfusion of high-oxygen (21%) Krebs-bicarbonate solution (HKS) onto rat sciatic nerves significantly constricted the epineurial arterioles in a time-dependent manner. The HKS-induced constriction of the epineurial arterioles was significantly reduced by treatment with 120 U/ml superoxide dismutase (SOD) alone or 5,000 U/ml catalase alone. In the presence of 120 U/ml SOD plus 5,000 U/ml catalase, 10(-4) M tempol, 10(-6) M diphenyleneiodium, 2 x 10(-4) M apocynin, or 10(-6) M allopurinol, the HKS-induced constriction of the epineurial arterioles completely disappeared. These results suggest that superfusion of highly oxygenated solution onto rat sciatic nerves constricts the epineurial arterioles through reactive oxygen species (ROS), including superoxide and hydrogen peroxide, and that production of superoxide involves a NADPH oxidase- or xanthine oxidase-dependent pathway. In conclusion, ROS play significant roles in the regulation of microcirculation of rat sciatic nerves in vivo.