Obligatory role of no in glutamate-dependent hyperemia evoked from
cerebellar parallel fibers.
Yang, Guang, and Costantino Iadecola.
Laboratory of Cerebrovascular Biology and Stroke, University of
Minnesota Medical School, Minneapolis, MN 55455
APStracts 3:0427R, 1996.
Electrical stimulation of the cerebellar parallel fibers (PF)
increases cerebellar blood flow (BFcrb), a response that is
attenuated by glutamate receptor antagonists and nitric oxide
synthase (NOS) inhibitors. In this study we investigated whether
administration of NO donors could counteract the attenuation by NOS
inhibitors of the vasodilation produced by PF stimulation. In
halothane-anesthetized rats, the cerebellar cortex was exposed and
superfused with Ringer solution. PF were stimulated with
microelectrodes (100 [mu]A, 30 Hz) and BFcrb recorded by a laser
-Doppler probe. During Ringer superfusion, PF stimulation increased
BFcrb by 56+/-7% and hypercapnia by 72+/-5% (n=5). Superfusion with
the non-selective NOS inhibitor L-NA (1 mM) reduced resting BFcrb and
attenuated the response to PF stimulation (-47+/-5%) and hypercapnia
(-46+/-7%; pCO2=50-60 mmHg). After L-NA, superfusion with the NO
donors 3-morpholino sydnonimine (SIN1; 100 [mu]M; n=5) or S-nitroso
-N-acetylpenicillamine (SNAP; 5 [mu]M; n=5) re-established resting
BFcrb (p>0.05 from before L-NA) and reversed the L-NA-induced
attenuation of the response to hypercapnia (p>0.05 from before
L-NA) but not to PF stimulation (p>0.05 from after L-NA).
Similar results were obtained when NOS activity was inhibited with
the inhibitor of neuronal NOS 7-nitroindazole (50 mg/kg; i.p.). Like
NO donors, the cGMP analogue 8br-cGMP (n=5), administered after L-NA,
restored resting BFcrb and counteracted the inhibition of the
response to hypercapnia but not PF stimulation. In contrast to NO
donors and 8br-cGMP, the NO-independent vasodilator papaverine (100
[mu]M; n=5) had no effect on the attenuation of the responses to
either PF stimulation or hypercapnia. Thus, NO donors are unable to
reverse the effect of NOS inhibition on the 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 the vasodilation produced by increased functional activity in the
cerebellar cortex.
Received 19 August 1996; accepted in final form 17 October 1996.
APS Manuscript Number R486-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996