Zenina T A, Golubeva L Iu, Saltykova V A, Manukhina E B, Mikoian V D, Kubrina L N, Vanin A F, Malyshev I Iu
Research Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia.
Izv Akad Nauk Ser Biol. 1998 Jul-Aug(4):506-12.
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.
关于机体对缺氧抗性的一氧化氮（NO）相关机制的研究表明：（1）急性缺氧会诱导大脑中NO过量产生，而不影响肝脏中NO的产生；（2）对缺氧的适应会降低肝脏和大脑中NO的产生；（3）对缺氧的适应可防止大脑中NO过量产生，并在急性缺氧期间增强肝脏中NO的合成。一种NO供体——二亚硝基铁配合物（DCI，200微克/千克，单次静脉注射）会使动物对急性缺氧的抗性降低30%，而引入一种NO合酶抑制剂——N-硝基-L-精氨酸（NNA，50微克/千克，单次腹腔注射）和一种NO捕获剂——二乙基二硫代氨基甲酸盐（DETC，200毫克/千克，单次腹腔注射），分别会使抗性提高1.3倍和2倍。对缺氧的适应是在肝脏和大脑中热休克蛋白HSP70积累的背景下实现的。用DCI进行疗程治疗可重现对缺氧适应的抗缺氧效果。在适应缺氧过程中用NNA进行疗程治疗可阻止HSP70的积累以及抗缺氧效果的发展。因此，NO以及依赖NO的HSP70合成激活在对缺氧的适应中起重要作用。
