IMPORTANCE OF NITRIC-OXIDE FOR LOCAL INCREASES OF BLOOD-FLOW IN RAT CEREBELLAR CORTEX DURING ELECTRICAL-STIMULATION

The endothelium-derived relaxing factor, probably nitric oxide (NO), I s a potent vasodilator that regulates the vascular tone in several vas cular beds, including the brain. We explored the possibility that NO m ight be of importance for the increase of cerebral blood dow (CBF) ass ociated with activity of the well-defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry was used to measure increa ses of cerebellar blood flow evoked by trains of electrical stimulatio ns of the dorsal surface. The evoked increases of CBF were frequency-d ependent, being larger on than off the parallel fiber tracts, suggesti ng that conduction along parallel fibers and synaptic activation of ta rget cells were important for the increase of CBF. This was verified e xperimentally since the evoked CBF increases were abolished by tetrodo toxin and reduced by 10 mM Mg2+ and selective antagonists for non-N-me thyl-D-aspartate receptors. The cerebellar cortex contains high levels of NO synthase. This raised the possibility that NO was involved in t he increase of CBF associated with neuronal activation. NO synthase in hibition by topical application of N-G-nitro-L-arginine attenuated the evoked CBF increase by about 50%. This effect was partially reversed by pretreatment with L-arginine, the natural substrate for the enzyme, while NG-nitro-D-arginine, the inactive enantiomer, had no effect on the evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspa rtate receptors and NO synthase had no further suppressing effect on t he blood now increase than either substance alone, suggesting that the NO-dependent now rise was dependent on postsynaptic mechanisms. These findings are consistent with the idea that local synthesis of NO is i nvolved in the transduction mechanism between neuronal activity and in creased CBF.