Nitric oxide has various actions, acting in a neurotransmitter-like role an
d also as a paracrine messenger between vascular endothelial and smooth mus
cle cells. This study was done to determine whether endogenous nitric oxide
has a role in modulating evoked catecholamine release from the canine adre
nal medulla. Isolated adrenal glands were perfused with Krebs-Ringer soluti
on as a control, or with Krebs-Ringer solution containing either N-G-monome
thyl-L-arginine (L-NMMA: 3 x 10(-4) M) to non-selectively inhibit nitric ox
ide synthase or 7-nitroindazole (10(-4) M), a relatively selective inhibito
r of neuronal nitric oxide synthase. Catecholamine release was evoked using
the nicotinic cholinergic agonist 1,1-dimethyl-4-phenylpiperazinium iodine
. From the collected perfusate epinephrine. norepinephrine, and dopamine we
re measured by high performance liquid chromatography. Previous studies hav
e shown that in the presence of L-NMMA, basal releases of epinephrine. nore
pinephrine and dopamine are increased. 7-Nitroindazole had no effect on bas
al catecholamine release, suggesting that nitric oxide from an endothelial
source was responsible for the inhibition of basal catecholamine release fr
om the adrenal medulla. Epinephrine and norepinephrine releases were augmen
ted when either of the nitric oxide synthase inhibitors was added during su
bmaximal nicotinic stimulation, indicating that endogenous nitric oxide inh
ibited release of epinephrine and norepinephrine. Both neuronal and endothe
lial nitric oxide synthases appeared to be responsible for this inhibition.
In summary. these studies suggest that nitric oxide. from both neuronal and
endothelial sources, modulates evoked catecholamine release from canine ad
renal medulla, while nitric oxide from an endothelial source is most likely
responsible for modulation of catecholamine release under basal conditions
. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.