Acetylcholine-induced relaxation and contraction of rat tail artery: Role of muscarinic receptor subtypes

Acetylcholine (Ach)-dose responses were observed in phenylephrine- contracted perfused segments of the rat tail artery in the presence or absence of muscarinic receptor subtype antagonists [pirenzepine, M1; gallamine, M2 or 4-diphenylacetoxy N-methylpiperidine methiodide (4-DAMP), M3]. Dose responses to each antagonist was also observed in the presence or absence of Ach. Arterial endothelium was either left intact, denuded with saponin or was treated with L-NAME (ω-nitro-L-arginine methyl ester). In endothelium-intact preparations, Ach-induced relaxation was unaffected by gallamine, but was completely or partially reversed by pirenzepine or 4- DAMP, respectively. The antagonistic effects of pirenzepine and 4-DAMP were not observed in endothelium-denuded preparations. In some tissues, the M1 agonist 4-[[[(3chlorophenyl) amino] carbonyl] oxy]-N,N,N-trimethyl-2-butyn- 1-aminium chloride (McN-A-343) slightly enhanced Ach relaxation at low doses but caused contraction at higher doses. It is concluded that M1 and M3 receptors are located on the endothelium; while the M3 mediates relaxation, M1 contributes a minor role.