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 · kg¹ · min¹) or its selective antagonist adrenomedullin-(2252) (5, 15, and 50 ng · kg¹ · min¹). Proadrenomedullin NH₂-terminal 20 peptide (PAMP; 5, 15, and 50 ng · kg¹ · min¹) 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.

proadrenomedullin-derived peptides; acetylcholine; splanchnic nerve stimulation; adrenal gland