Effects of inhibition of neuronal nitric oxide synthase on NMDA-induced changes in cerebral blood flow and oxygen consumption

Abstract.

This study was performed to determine whether neuronal nitric oxide synthase (nNOS) is involved in altering regional cerebral blood flow (rCBF) and oxygen consumption during N-methyl-D-aspartate (NMDA) receptor stimulation. A craniotomy was performed in rats, under isoflurane anesthesia, to expose the cerebral cortex. For the control group (n=7), an NMDA patch (10^–3 M) was applied to the exposed cortex (ipsilateral cortex, IC) for 10 min before determining rCBF and O₂ consumption. The patch was changed every 5 min. To block nNOS, 7-nitroindazole (7-NI, 25 mg/kg i.p.) was administered 30 min before NMDA application (7-NI group, n=7). The autoradiographic technique was used to determine rCBF and regional O₂ consumption was measured using cryomicrospectrophotometry. Blood pressure, heart rate, blood gases, and hemoglobin were similar between the two groups. In the control group, rCBF (108±32 ml/100 g per min) and O₂ consumption (4.8±0.8 ml O₂/100 g per min) of the IC where NMDA was applied were higher than those of the contralateral cortex (CC) (78±16 ml/100 g per min and 3.1±0.4 ml O₂/100 g per min, respectively). Neither rCBF nor O₂ consumption of the IC of the 7-NI group was statistically different from that of the CC. However, O₂ consumption of the IC of the 7-NI group was lower (3.9±1.0 ml O₂/100 g per min) than that of the IC of the control group. Our data demonstrated that a direct cortical application of NMDA increased O₂ consumption and rCBF, and that pretreatment with 7-NI not only attenuated the effects of NMDA on rCBF but also decreased the O₂ consumption during NMDA receptor stimulation.