Effects of pirenzepine and hexamethonium on adrenal catecholamine release in responses to endogenous and exogenous acetylcholine in anesthetized dogs.

Abstract

We investigated the way in which hexamethonium and pirenzepine, a selective muscarinic (M) 1 receptor antagonist, modify the release of catecholamines from dog adrenal gland in response to endogenous and exogenous acetylcholine (ACh) in vivo. Output of epinephrine (EPI), and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. Intraarterial (i.a.) injections of ACh (1.5 and 3 micrograms) or muscarine (3 and 6 micrograms) into the phrenicoabdominal artery and splanchnic nerve stimulation (SNS, 3 Hz) produced marked increases in EPI and NE output. Hexamethonium (1 mg/kg intravenously, i.v.) inhibited the increases in EPI and NE output in response to exogenous ACh and SNS. Pirenzepine (10 micrograms/kg i.v.) inhibited the ACh-induced increases in EPI and NE output but did not modify the SNS-induced increases. The muscarine-induced increases in EPI and NE output were also inhibited by pirenzepine. These results indicate that the exogenous ACh-induced release of adrenal catecholamines is mediated through both nicotinic and M1 receptors, in contrast to the predominant mediation of nicotinic receptors in response to endogenous ACh.