Permissive and obligatory roles of nitric oxide in cerebro-vascular
responses to hypercapnia and acetylcholine.
Iadecola, Costantino, and Fangyi Zhang.
Laboratory of Cerebrovascular Biology and Stroke, Department of
Neurology, University of Minnesota Medical School, Minneapolis, MN
55455
APStracts 3:0158R, 1996.
Inhibition of nitric oxide (NO) synthesis attenuates the hypercapnic
cerebrovasodilation or the increases in cerebral blood flow (CBF)
produced by acetylcholine, either topically applied or endogenously
released in neocortex by stimulation of the basal forebrain
cholinergic system. We investigated whether exogenous administration
of NO, using NO donors, can reverse the attenuation of these
responses by NO synthase (NOS) inhibitors. In halothane-anesthetized,
ventilated rats the frontoparietal cortex was exposed and superfused
with Ringer. CBF was monitored at the superfusion site by laser
-Doppler flowmetry. The basal forebrain was stimulated (100 A-50 Hz)
with microelectrodes stereotaxically implanted. Superfusion with the
NOS inhibitor nitro-L-arginine (L-NA; 1 mM) reduced resting CBF (-38
2%; mean SE) and attenuated the vasodilation elicited by hypercapnia
(pCO2: 50-60 mmHg; -79 3%), acetylcholine (10 M; -83 7%) or basal
forebrain stimulation (-44 2%) (p<0.05 analysis of variance and Tukey
s test). After L-NA, topical application of 3-morpholinosydnonimine
(SIN-1)(n=7), S-nitroso-N-acetylpenicillamine (SNAP) (n=6) or 8
-Bromo-cGMP (n=4) re-established resting CBF (p>0.05 from Ringer)
and reversed the attenuation of the response to hypercapnia
(p>0.05 from Ringer). However, SIN-1 or SNAP failed to reverse
the attenuation of the response to basal forebrain stimulation or
topical acetylcholine (p>0.05 form L-NA). After L-NA, the NO
-independent vasodilator papaverine (n=4) re-established resting CBF
(p>0.05 from Ringer) but failed to restore the hypercapnic
vasodilation (p>0.05 from L-NA). The attenuation of hypercapnic
response by the neuronal NOS inhibitor 7-nitroindazole was
counteracted only partially by SIN-1 (n=4) or 8-bromo-cGMP (n=4). The
data support the hypothesis that the vasodilation elicited by
hypercapnia requires resting levels of NO for its expression, while
the response to endogenous or exogenous acetylcholine depends on
agonist-induced NOS activation. In hypercapnia NO may act as a
permissive factor by facilitating the action of other vasodilators,
while in the vascular response initiated by acetylcholine NO is
likely to be the major mediator of smooth muscle relaxation.
Received 26 February 1996; accepted in final form 11 April 1996.
APS Manuscript Number R113-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96