Uncoupling of flow and metabolism induced by sodium nitroprusside in rat cerebral cortex

The effects of sodium nitroprusside (SNP) on cerebral blood flow and glucose metabolism were investigated by the microinfusion of SNP into rat cerebral cortex. A significant enhancement in glucose metabolism, as measured using [14C]deoxyglucose (DG), was observed throughout widespread areas of the cerebral cortex within 1 h of microinjection of 50 nmol/microl SNP. Using a kinetic analysis, the increase in glucose metabolism was found to be due to an increase in the phosphorylation of [14C]DG in the brain. On the other hand, regional cerebral blood flow, as measured using [14C]iodoantypirine, was not significantly altered by the SNP infusion. No significant cell death was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining 1 h after the SNP infusion. The uncoupling of flow and metabolism was almost completely prevented by pretreatment with an NMDA antagonist, MK-801. However, pretreatment with MK-801 did not prevent the SNP-induced neural cell death detected 6 h after the SNP infusion. These results suggest that the SNP-induced uncoupling of flow and metabolism was not directly related to neural cell death in the cerebral cortex.