Nitric oxide modulates evoked catecholamine release from canine adrenal medulla

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.