LOCAL UNCOUPLING OF THE CEREBROVASCULAR AND METABOLIC RESPONSES TO SOMATOSENSORY STIMULATION AFTER NEURONAL NITRIC-OXIDE SYNTHASE INHIBITION

It has recently been shown, using either genetically engineered mutant mice (nitric oxide synthase [NOS] knockout) or specific pharmacologic al tools, that type I NOS (neuronal isoform of NOS, [nNOS]) participat es in coupling cerebral blood flow to functional activation. However, it has not been clearly established whether the associated metabolic r esponse was preserved under nNOS inhibition and whether this action wa s exerted homogeneously within the brain. To address these issues, we analyzed the combined circulatory and metabolic consequences of inhibi ting the nNOS both at rest and during functional activation in the rat anesthetized with alpha-chloralose. Cerebral blood flow and cerebral glucose use (CGU) were measured autoradiographically using [C-14]iodoa ntipyrine and [C-14]2-deoxyglucose during trigeminal activation induce d by unilateral whiskers stimulation in vehicle- and 7-nitroindazole-t reated rats. Our data show that inhibition of nNOS globally decreased CBF without altering CGU, indicating that NO-releasing neurons play a significant role in maintaining a resting cerebrovascular tone in the whole brain. During whisker stimulation, nNOS inhibition totally aboli shed the cerebrovascular response only in the second order relay stati ons (thalamus and somatosensory cortex) of the trigeminal relay withou t altering the metabolic response. These findings provide evidence tha t the involvement of neurally-derived NO in coupling flow to somatosen sory activation is region-dependent, and that under nNOS inhibition, C BF and CGU may vary independently during neuronal activation.