title: 7-Nitroindazole attenuates vasodilation from cerebellar parallel fiber stimulation but not acetylcholine.
abstract: We used the relatively selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (7-NI) to test the hypothesis that the increases in local cerebellar blood flow (BFcrb) elicited by activation of the cerebellar parallel fibers (PF) are mediated by neuronal production of nitric oxide. In halothane-anesthetized rats, the cerebellar cortex was exposed and superfused with Ringer solution (37 degrees C; pH 7.3-7.4). The PF were stimulated electrically (100 microA, 30 Hz, 40 s), while BFcrb was monitored at the site of stimulation by a laser-Doppler flow probe. In vehicle-treated rats (n = 5), PF stimulation increased BFcrb by 61 +/- 5% (P < 0.05; analysis of variance and Tukey's test). 7-NI attenuated the increase in BFcrb dose dependently (10-100 mg/kg i.p.; n = 5 animals/dose) and by 55 +/- 7% at 100 mg/kg (P < 0.05). The attenuation of the response to PF stimulation was correlated with the degree of inhibition of calcium-dependent brain nitric oxide synthase activity, measured ex vivo by the citrulline assay (n = 21). 7-NI also attenuated the cerebrovasodilation elicited by hypercapnia (PCO2 = 50-60 mmHg) but did not affect the vasodilation evoked by acetylcholine (10 microM; n = 4; P > 0.05; t-test), a response mediated by endothelial nitric oxide synthase. 7-NI did not attenuate the BFcrb increase evoked by the nitric oxide donor S-nitroso-N-acetylpenicillamine (1 mM; n = 5; P > 0.05; t-test). Similarly, 7-NI did not affect resting systemic arterial pressure. These observations suggest that selective inhibition of neuronal nitric oxide synthase by 7-NI attenuates the increases in BFcrb evoked by PF stimulation. The findings provide additional support to the hypothesis that the increase in BFcrb evoked by PF stimulation is mediated, in part, by glutamate-induced activation of neuronal nitric oxide synthase.
authors.affiliation: Laboratory of Cerebrovascular Biology and Stroke, University of Minnesota Medical School, Minneapolis 55455, USA.
authors.forename: C
authors.initials: C
authors.lastname: Iadecola
authors.forename: G
authors.initials: G
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Xu
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D004558:Electric Stimulation; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D007191:Indazoles; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C080122:7-nitroindazole