Study On The Combined Effects Of Hypoxia And Soman Intoxication On Cholinergic Signal Transduction In Rats Heart

Soman, an organophosphate compound, famous for its high toxicity in animals and human beings, difficulty in prevention and treatment, is one of the chemical warfare agents with a large military stock. The combined injury of hypoxia and soman poisoning is a kind of specific chemical injury which maybe occurs in the high altitude area. In previous studies we found that the toxicity of soman was increased by hypoxia exposure but the mechanism was not clearly underlined. In present study, we established the model of the combined injury of hypoxia in simulated high altitude and soman intoxication in whole animals. With various techniques of RT-PCR, Western blot, biochemical analysis and so on, the combined injury of hypoxia and soman poisoning and its mechanisms were investigated. Based on the results of our studies, we can draw following conclusions: ①AChE activity and the expression of M2 receptor mRNA were decreased by soman poisoning. However, the inhibitory effect of soman on heart AChE activity was slightly reduced by hypoxia exposure, the expression of M2 receptor mRNA in the rat heart was also significantly up-regulated by the combined injury of soman intoxication and hypoxia exposure. ②Simulated high altitude hypoxia had hardly no effects on the expression of Giα protein. Otherwise, Giα expression was suppressed by soman intoxication and combined treatments. ③in the rat heart studied in this project, increased AC activity, PKA activity and cAMP concentration were discovered respectively inthe animals treated by soman only and treated by combined injury, but decreased AC activity and cAMP concentration were discovered in the animals treated by hypoxia exposure only. The toxicity of soman was markedly increased by hypoxia exposure. These results strongly suggest a enhancing effect of soman poisoning combined with hypoxia on heart cholinergic signal transduction system confirmed by M receptor up-regulated, Giα expression suppress, cAMP formation and PKA activity increase. Furthermore, this enhancement maybe play an important role in the mechanism of heart injury induced by soman intoxication in the altitude.