[NO-Dependent mechanisms of adaptation to hypoxia].
Studies of nitrogen oxide (NO)-dependent mechanisms of organism resistance to hypoxia demonstrate that (1) acute hypoxia induces NO hyperproduction in the brain and does not affect NO production in the liver; (2) adaptation to hypoxia decreases NO production in the liver and brain; and (3) adaptation to hypoxia prevents NO hyperproduction in the brain and enhances NO synthesis in the lever during acute hypoxia. An NO donor--dinytrosyl iron complexes (DCI, 200 micrograms/kg, single intravenous (i.v.) introduction)--decreases animal resistance to acute hypoxia by 30%, while introduction of an NO synthase inhibitor--N- nitro-L-arginine (NNA, 50 micrograms/kg, single intraperitoneal (i.p.) introduction)--and an NO trap--diethyldithiocarbamate (DETC, 200 mg/kg, single i.p. introduction)--increases the resistance 1.3 and 2 times, respectively. Adaptation to hypoxia is realized against a background of accumulation of heat shock proteins HSP70 in the liver and brain. Course treatment with DCI reproduces the antihypoxic effect of adaptation to hypoxia. Course treatment 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 adaptation to hypoxia.
Zenina
T A
TA
Research Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia.
Golubeva
L Iu
LIu
Saltykova
V A
VA
Manukhina
E B
EB
Mikoian
V D
VD
Kubrina
L N
LN
Vanin
A F
AF
Malyshev
I Iu
IIu
D000208:Acute Disease; D000222:Adaptation, Physiological; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007501:Iron / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D009589:Nitrogen Oxides; D019335:Nitroarginine; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D004050:Ditiocarb; D007501:Iron; D019001:Nitric Oxide Synthase