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Am J Physiol Heart Circ Physiol 285: H298-H304, 2003. First published March 6, 2003; doi:10.1152/ajpheart.00043.2003
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Attenuation of activity-induced increases in cerebellar blood flow in mice lacking neuronal nitric oxide synthase

Guang Yang, Yi Zhang, M. Elizabeth Ross, and Costantino Iadecola

Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021

Submitted 16 January 2003 ; accepted in final form 4 March 2003

We used mice deficient in neuronal nitric oxide (NO) synthase (nNOS) to specifically investigate the role of neuronal NO in the increase of cerebellar blood flow (BFcrb) produced by neural activation. Crus II, a region of the cerebellar cortex that receives trigeminal sensory afferents, was activated by low-intensity stimulation of the upper lip (5–25 V, 4–16 Hz) in anesthetized mice. BFcrb was recorded in Crus II by using a laser-Doppler flow probe. In wild-type mice, upper lip stimulation increased BFcrb in the Crus II by 28 ± 3% (25 V, 10 Hz, n = 6). The rise in BFcrb was attenuated by 73 ± 3% in nNOS-/- mice (P < 0.05, n = 6). The increases in BFcrb produced by superfusion of Crus II with glutamate or by systemic administration of harmaline were also attenuated in nNOS-/- mice (P < 0.05). In contrast, the increases in BFcrb produced by topical superfusion of Crus II with acetylcholine or adenosine and the increase in BFcrb produced by hypercapnia were not affected (P > 0.05). The field potentials evoked in the Crus II by upper lip stimulation did not differ between wild-type and nNOS-null mice. These data provide the first nonpharmacological evidence that nNOS-derived NO is a critical link between glutamatergic synaptic activity and blood flow in the activated cerebellum.

cerebral circulation; cerebellum; laser-Doppler flowmetry; vasodilation; glutamate


Address for reprint requests and other correspondence: C. Iadecola, Div. of Neurobiology, 411 E. 69th St., Rm. KB410, New York, NY 10021 (E-mail: coi2001{at}med.cornell.edu).




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