We examined the effects of sarafotoxin 6c (S6c), an endothelin-B (ET_B) receptor agonist, on adrenal catecholamine secretion in response to cholinergic stimuli in pentobarbital sodium-anesthetized dogs. Drugs were administered intra-arterially into the adrenal gland through the phrenicoabdominal artery. Infusion of S6c attenuated increases in adrenal catecholamine output induced by splanchnic nerve stimulation. The inhibitory effect of S6c on the catecholamine secretion response was suppressed with a selective ET_B receptor antagonist N-cis 2,6-dimethylpiperidinocarbonyl-L--methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (BQ-788), a nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester, and a neuronal NOS inhibitor 7-nitroindazole monosodium salt (7-NINA). Similar results were obtained with the catecholamine secretion response induced by injection of ACh. 7-NINA alone did not affect these catecholamine secretion responses. These results suggest that ET_B receptors play an inhibitory role in adrenal catecholamine secretion by activating neuronal NOS, whereas neuronal NOS is unlikely to be involved in regulation of adrenal catecholamine secretion in the absence of simultaneous ET_B receptor stimulation.