NO-DEPENDENT MECHANISMS OF ADAPTATION TO HYPOXIA

Studies of nitrogen oxide (NO)-dependent mechanisms of organism resist ance to hypoxia demonstrate that (1) acute hypoxia induces NO hyperpro duction in the brain acid does not affect NO production in the liver; (2) adaptation to hypoxia decreases NO production in the liver and bra in; and (3) adaptation to hypoxia prevents NO hyperproduction in the b rain and enhances NO synthesis in the lever during acute hypoxia. An N O donor-dinytrosyl iron complexes (DCI, 200 mu g/kg, single intravenou s (i/v) introduction)-decreases animal resistance to acute hypoxia by 30%, while introduction of an NO synthase inhibitor-N-nitro-L-arginine (NNA, 50 mu g/kg, single intraperitoneal (i/p) introduction)-and an N O trap-diethyldithiocarbamate (DETC, 200 mg/kg, single i/p introductio n)-increases the resistance 1.3 and 2 times, respectively. Adaptation to hypoxia is realized against a background of accumulation of heat sh ock proteins HSP70 in the liver and brain. Course treatment with DCI r eproduces the antihypoxic effect of adaptation to hypoxia. Course trea tment with NNA during adaptation to hypoxia prevents both accumulation of HSP70 and development of the antihypoxic effect. Hence, NO and NO- dependent activation of HSP70 synthesis play an important role in adap tation to hypoxia.