Endothelium-derived nitric oxide (NO) plays an important role in regulating vascular tone. Lack of NO bioavailability can result in cardiovascular disease. NO bioavailability is determined by its rates of generation and catabolism; however, it is not known how the NO catabolism rate is regulated in the vascular wall under normoxic, hypoxic and anaerobic conditions. To investigate NO catabolism under different oxygen concentrations, studies of NO and O₂ consumption by the isolated rat aorta were performed using electrochemical sensors. Under normoxic conditions, the rate of NO consumption in solution was enhanced in the presence of a rat aorta. Under hypoxic conditions, NO consumption decreased in parallel with the [O₂]. Like the inhibition of mitochondrial respiration by NO, the inhibitory effects of NO on aortic O₂ consumption increased as O₂ concentration decreased. Under anaerobic conditions, however, a paradoxical reacceleration of NO consumption occurred. This increased anaerobic NO consumption was inhibited by the cytochrome c oxidase inhibitor NaCN, but not by the free iron chelator deferoxamine (DFO), the flavoprotein inhibitor diphenylene iodonium (DPI, 10 µM), or superoxide dismutase (SOD, 200 U/mL). The effect of O₂ on the NO consumption could be reproduced by purified cytochrome c oxidase (CcO), implying CcO is involved in the aortic NO catabolism. This reduced NO catabolism at low O₂ tensions supports the maintenance of effective NO levels in the vascular wall, reducing the resistance of blood vessels. The increased anaerobic NO catabolism may be important for removing excess NO accumulation in ischemic tissues.