Gutsaeva D R, Moskvin A N, Zhilyaev S Yu, Kostkin V B, Demchenko I T
I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 M. Torez Prospekt, 194223 St. Petersburg, Russia.
Neurosci Behav Physiol. 2005 Sep;35(7):751-6. doi: 10.1007/s11055-005-0119-9.
The hypothesis that in conditions of hyperbaric oxygenation, nitric oxide (NO) modulates the vasodilatory effect of CO2 in the brain and thus accelerates the neurotoxic action of oxygen was verified experimentally. Conscious rats breathed atmospheric air or oxygen at 5 atm and blood flow in the striatum was measured before and after inhibition of carbonic anhydrase with acetazolamide, which causes retention of CO2 in the brain. Acetazolamide (35 mg/kg) increased blood flow in the animals when breathing air by 38 +/- 7.4% (p < 0.01), while preliminary inhibition of NO synthase with N(omega)-nitro-L-arginine-methyl ester (L-NAME, 30 mg/kg) significantly weakened its vasodilatory action. Inhibition of carbonic anhydrase in animals breathing hyperbaric oxygen at 5 atm prevented cerebral vasoconstriction, increased brain blood flow, and accelerated the development of oxygen convulsions. The vasodilatory effect of acetazolamide in hyperbaric oxygenation was significantly reduced in animals pretreated with the NO synthase inhibitor, such that the latent period of convulsions increased. The results obtained here provide evidence that in conditions of extreme hyperoxia, NO modulates the cerebral hyperemia developing in conditions of CO2 retention in the brain and accelerates the development of the neurotoxic actions of hyperbaric oxygen.
有假说认为，在高压氧环境下，一氧化氮（NO）可调节大脑中二氧化碳的血管舒张作用，从而加速氧气的神经毒性作用。本研究通过实验对此假说进行了验证。清醒大鼠呼吸常压空气或5个大气压的氧气，在用乙酰唑胺抑制碳酸酐酶前后测量纹状体的血流，乙酰唑胺可导致大脑中二氧化碳潴留。乙酰唑胺（35mg/kg）使呼吸空气的动物血流增加38±7.4%（p<0.01），而预先用N（ω）-硝基-L-精氨酸甲酯（L-NAME，30mg/kg）抑制一氧化氮合酶可显著减弱其血管舒张作用。在呼吸5个大气压高压氧的动物中抑制碳酸酐酶可防止脑血管收缩，增加脑血流量，并加速氧惊厥的发生。在用一氧化氮合酶抑制剂预处理的动物中，乙酰唑胺在高压氧环境下的血管舒张作用显著降低，惊厥潜伏期延长。本研究结果表明，在极端高氧环境下，NO可调节大脑中二氧化碳潴留时出现的脑充血，并加速高压氧神经毒性作用的发展。
