| Popis: |
The level of adenosinetriphosphate (ATP) in the cerebral cortex of rats was shown to be decreased on exposure to hypoxic conditions (4% O 2 , 0.05% CO 2 , 95.95% N 2 ). This effect of hypoxia was markedly inhibited by subhypotensive doses of indoramin (Wy 21901) and by dihydroergotoxine and naftidrofuryl. Slight inhibition was produced by prazosin, piracetam, phentolamine and clonidine. None of these drugs altered the ATP levels of rats exposed to normal oxygen levels (20%). A variety of other drugs including meclofenoxate, pemoline, diazepam and diphenhydramine were without effect on hypoxic ATP levels. Results of in vitro experiments indicated that indoramin increased the rate of synthesis of ATP whereas dihydroergotoxine decreased the rate of utilisation under hypoxic conditions. Under the same conditions naftidrofuryl stimulated ATP synthesis and slightly inhibited the rate of utilisation. It is probable that these different effects on the turnover of ATP were responsible for the similar effects of the drug observed in vivo on cerebral ATP levels. In a further series of in vitro experiments the rate of swelling of synaptosomes on exposure to hypoxic conditions was shown to be reduced by the addition of indoramin, dihydroergotoxine and naftidrofuryl. Cerebral microvessels behaved similarly. The degree of whole brain swelling in animals exposed to hypoxia was less in indoramin treated animals than in controls. In anaesthetised rats indoramin and naftidrofuryl protected against cyanide induced reductions in EEG voltage, whereas dihydroergotoxine was inactive. These data are consistent with the actions described on ATP synthesis and utilisation. Overall, indoramin resembled dihydroergotoxine and naftidrofuryl, agents used widely in cerebro-vascular disease, in maintaining high energy phosphate levels under adverse conditions. |
