Sakai N, Mizuno R, Ono N, Kato H, Ohhashi T. High oxygen tension constricts epineurial arterioles of the rat sciatic nerve via reactive oxygen species. Am J Physiol Heart Circ Physiol 293: H1498-H1507, 2007. First published May 18, 2007; doi:10.1152/ajpheart.01190.2006.-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 2ϩ -channel blocker, caused a dosedependent 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 Ϫ4 M tempol, 10 Ϫ6 M diphenyleneiodium, 2 ϫ 10 Ϫ4 M apocynin, or 10 Ϫ6 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. peripheral nerves; microcirculation; superoxide; hydrogen peroxide BLOOD SUPPLY TO PERIPHERAL nerves is important to maintain the functions of the nerve fibers. The disturbance of blood circulation within sciatic nerves produces dysfunction such as suppression of motor nerve conduction velocity (2, 3). It has become clear that pathogenesis of diabetic neuropathy is associated with a reduction of blood flow in sciatic nerves in diabetic animals and humans (14, 34). Thus understanding the regulation of blood flow in sciatic nerves is quite important for diagnosis and treatment of diabetic neuropathy.Laser Doppler flowmetry and hydrogen clearance are methods available to study the blood flow in sciatic nerves in vivo (2-4, 16, 17, 30, 33, 35, 46). From the use of these methods, it is known that the epineurial and endoneurial arterioles of sciatic nerves play crucial roles in the regulation of microcirculation. Although these methods are capable of measuring local blood flow in the sheath of sciatic nerves in vivo, changes in the diameter of the arterioles in the sheath of sciatic nerves could not be identified. It is necessary to measure changes in the diameter of the arterioles in vivo, because the arterioles and small arteries are resistant vessels, and changes in the...