We examined the role of nitric oxide (NO) in adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS) and exogenous acetylcholine (ACh) in anesthetized dogs. The NO synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME), NO donor 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)- N-methyl-1-propanamine (NOC 7), and ACh were administered intra-arterially into the adrenal gland. The increases in catecholamine output induced by ACh (0.75–3 μg) were enhanced byl-NAME (0.1–1 mg/min) and inhibited by NOC 7 (0.2–2 μg/min). Inhibition by NOC 7 (2 μg/min) was observed during treatment withl-NAME (1 mg/min). The increases in catecholamine output induced by SNS (1–2 Hz) were inhibited byl-NAME and by NOC 7. No inhibitory effect of NOC 7 was observed during treatment withl-NAME. These results suggest that NO may play an inhibitory role in the regulation of adrenal catecholamine secretion in response to exogenous ACh.

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We examined the effects of proadrenomedullin-derived peptides on the release of adrenal catecholamines in response to cholinergic stimuli in pentobarbital sodium-anesthetized dogs. Drugs were administered into the adrenal gland through the phrenicoabdominal artery. Splanchnic nerve stimulation (1, 2, and 3 Hz) and ACh injection (0.75, 1.5, and 3 μg) produced frequency- or dose-dependent increases in adrenal catecholamine output. These responses were unaffected by infusion of adrenomedullin (1, 3, and 10 ng ⋅ kg−1 ⋅ min−1) or its selective antagonist adrenomedullin-(22—52) (5, 15, and 50 ng ⋅ kg−1 ⋅ min−1). Proadrenomedullin NH2-terminal 20 peptide (PAMP; 5, 15, and 50 ng ⋅ kg−1 ⋅ min−1) suppressed both the splanchnic nerve stimulation- and ACh-induced increases in catecholamine output in a dose-dependent manner. PAMP also suppressed the catecholamine release responses to the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (0.5, 1, and 2 μg) and to muscarine (0.5, 1, and 2 μg), although the muscarine-induced response was relatively resistant to PAMP. These results suggest that PAMP, but not adrenomedullin, can act as an inhibitory regulator of adrenal catecholamine release in vivo.