Nitric oxide contributes to functional hyperemia in cerebellar cortex

C. Iadecola, J. Li, Timothy J Ebner, X. Xu

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70 Scopus citations


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 superfused with Ringer (37°C; pH 7.3-7.4). PF were stimulated electrically (100 μA; 30 Hz), and the associated changes in cerebellar cortex blood flow (BF(erb)) were monitored by laser-Doppler flowmetry. The field potentials evoked by PF stimulation were recorded using microelectrodes. During Ringer superfusion (n = 7), PF stimulation increased BF(erb) (+52 ± 4%). Topical application of the NO synthase (NOS) inhibitor N(ω)-nitro-L-arginine (L-NNA; 0.1-1 mM) attenuated the increases in BF(crb) 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 NOS catalytic activity, assessed ex vivo using the citrulline assay, by 95 ± 9% (P < 0.001). L-NNA did not influence the field potentials evoked by PF stimulation. D-NNA (1 mM; n = 6), the inactive stereoisomer of nitroarginine, did not attenuate the BF(crb) response (P > 0.05). Methylene blue (1 mM; n = 7) reduced the response by 41 ± 9% (P < 0.01) without affecting NOS catalytic activity (P < 0.05). The increases in BF(crb) were not affected by lesioning the NOS-containing nerve fibers innervating cerebral vessels, indicating that these nerves are not the source of NO. Thus the increases in BF(crb) 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 coupling of function activity to blood flow and support the hypothesis that NO is one of the mediators responsible for functional hyperemia in the central nervous system.

Original languageEnglish (US)
Pages (from-to)R1153-R1162
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5 37-5
StatePublished - 1995


  • N(ω)-nitro-L-arginine
  • cerebral circulation
  • field potentials
  • laser Doppler
  • nitric oxide synthase
  • parallel fibers


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