Downregulation of nitric oxide in the brain of mice during their hypoxic preconditioning.

An animal model of hypoxic preconditioning was produced in mice by repeated exposure to autohypoxic condition. The animals' tolerance times to hypoxia were 1.7, 1.8, 2.1, and 2.3 times longer in runs 2, 3, 4, and 5, respectively, than that in run 1, and their oxygen consumption and heart and respiration rates were progressively and significantly slowed down during the repetitive exposure to hypoxia. L-Arginine concentration, nitric oxide (NO) synthase-positive cells, NO synthase activity, and NO content in the whole brain and the subregions telencephalon, diencephalon, and brain stem were significantly increased during the first exposure and were, instead of continuing to increase, significantly decreased in run 4 after the second and third exposure. Tolerance times under the hypoxic condition were significantly shortened and prolonged when preadministration of L-arginine and its analog, respectively, was made. These results indicate that NO in the brain is downregulated under condition of hypoxic preconditioning and negatively involved in increased tolerance to hypoxia.