7-nitroindazole attenuates vasodilation from cerebellar parallel
fiber stimulation but not acetylcholine.
Iadecola, Costantino, Guang Yang, and Sherry Xu.
Laboratory of Cerebrovascular Biology and Stroke, University of
Minnesota Medical School, Minneapolis, MN 55455
APStracts 2:0316R, 1995.
We used the relatively selective inhibitors of neuronal nitric oxide
synthase 7-nitroindazole (7-NI) to test the hypothesis that the
increases in local 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 (37 C; pH=7.3-7.4). The
PF were stimulated electrically (100 [mu]A-30 Hz; 40 sec) 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 per 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 [mu]M; 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
(SNAP; 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.
Received 28 June 1995; accepted in final form 7 November 1995.
APS Manuscript Number R404-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95