NITRIC-OXIDE CONTRIBUTES TO FUNCTIONAL HYPEREMIA IN CEREBELLAR CORTEX

We used the parallel fibers (PF) system of the cerebellar cortex as a model to investigate the role of nitric oxide (NO) in the increases in blood flow elicited by neural activation. Rats were anesthetized with halothane and ventilated. The vermis was exposed, and the site was su perfused with Ringer (37 degrees C; pH 7.3-7.4). PF were stimulated el ectrically (100 mu A; 30 Hz), and the associated changes in cerebellar cortex blood flow (BFcrb) were monitored by laser-Doppler flowmetry. The field potentials evoked by PF stimulation were recorded using micr oelectrodes. During Ringer superfusion (n = 7), PF stimulation increas ed BFcrb (+52 +/- 4%). Topical application of the NO synthase (NOS) in hibitor N-omega-nitro-L-arginine (L-NNA; 0.1-1 mM) attenuated the incr eases in BFcrb dose dependently and by 50 +/- 4% at 1 mM (n = 9;P < 0. 001; analysis of variance and Tukey's test). L-NNA (1 mM) inhibited NO S catalytic activity, assessed ex vivo using the citrulline assay, by 95 +/- 9% (P < 0.001). L-NNA did not influence the field potentials ev oked by PF stimulation. D-NNA (1 mM; n = 6), the inactive stereoisomer of nitroarginine, did not attenuate the BFcrb response (P > 0.05). Me thylene blue (1 mM; n = 7) reduced the response by 41 +/- 9% (P < 0.01 ) without affecting NOS catalytic activity (P < 0.05). The increases i n BFcrb were not affected by lesioning the NOS-containing nerve fibers innervating cerebral vessels, indicating that these nerves are not th e source of NO. Thus the increases in BFcrb elicited by activation of PF are, in part, mediated by NO produced in the molecular layer during neural activity. The results indicated that NO participates in the co upling of function activity to blood flow and support the hypothesis t hat NO is one of the mediators responsible for functional hyperemia in the central nervous system.