OBLIGATORY ROLE OF NO IN GLUTAMATE-DEPENDENT HYPEREMIA EVOKED FROM CEREBELLAR PARALLEL FIBERS

Electrical stimulation of cerebellar parallel fibers (PF) increases ce rebellar blood flow (BFcrb), a response that is attenuated by glutamat e receptor antagonists and NO synthase (NOS) inhibitors. We investigat ed whether administration of NO donors could counteract attenuation by NOS inhibitors of vasodilation produced by PF stimulation. In halotha ne-anesthetized rats the cerebellar cortex was exposed and superfused with Ringer solution. PF were stimulated with microelectrodes (100 mu A, 30 Hz), and BFcrb was recorded by a laser-Doppler probe. During Rin ger superfusion, PF stimulation increased BFcrb by 56 +/- 7% and hyper capnia by 72 +/- 5% (n = 5). Superfusion with the nonselective NOS inh ibitor N-nitro-L-arginine (L-NNA, 1 mM) reduced resting BFcrb and atte nuated the response to PF stimulation (-47 +/- 5%) and hypercapnia (-4 6 +/- 7%; PCO2 = 50-60 mmHg). After L-NNA, superfusion with the NO don ors 3-morpholinosydnonimine (100 mu M, n = 5) or S-nitroso-N-acetyl-pe nicillamine (5 mu M, n = 5) reestablished resting BFcrb (P > 0.05 vs. before L-NNA) and reversed L-NNA-induced attenuation of the response t o hypercapnia (P > 0.05 vs. before L-NNA) but not PF stimulation (P > 0.05 vs. after L-NNA). Similar results were obtained when NOS activity was inhibited with the inhibitor of neuronal NOS 7-nitroindazole (50 mg/kg ip). Like NO donors, the guanosine 3',5'-cyclic monophosphate an alog 8-bromoguanosine 3',5'-cyclic monophosphate (n = 5), administered after L-NNA, restored resting BFcrb and counteracted inhibition of th e response to hypercapnia but not PF stimulation. In contrast to NO do nors and 8-bromoguanosine 3',5'-cyclic monophosphate, the NO-independe nt vasodilator papaverine (100 mu M, n = 5) had no effect on attenuati on of responses to PF stimulation or hypercapnia. Thus NO donors are u nable to reverse the effect of NOS inhibition on vasodilation produced by PF stimulation. The data support the hypothesis that the vascular response to PF stimulation, at variance with hypercapnia, requires NOS activation and NO production. Thus NO plays an obligatory role in vas odilation produced by increased functional activity in cerebellar cort ex.