Endothelial m, and m3 muscarinic receptor subtypes mediate acetylcholine - induced relaxation in rat tail artery

Abstract

The relaxation, by acetylchohne (ACh), of an agonist (eg phenylephnne: PE)-induced contraction is an accepted method for identifying a functional endothelmm in vascular tissues. The muscannic receptor subtype that mediates ACh-mduced relaxation varies from tissue to tissue and has not been identified in the ventral rat tail artery (RTA) We, therefore, investigated the receptor subtypes that are involved in ACh- induced relaxation of the RTA Perfused (2.5ml/min) segments (proximal third) of ventral RTAs from male SD-rats (300-350g) precontracted with PE (luM) were exposed to (a) graded concentrations of ACh in the presence or absence of muscannic receptor antagonists (pirenzepine (Pnz) for MI or 4-diphenylacetoxy-N-methylpipendine methiodide (4-DAMP) for M.) and (b): graded concentrations of a muscannic antagonist in the presence or absence of ACh Endothelium was either left intact or denuded with saponin or functionally inactivated with nitro-L-arginine methyl ester (L-NAME) ACh-induced relaxation was observed only in endothelmm- intact preparations but not in saponin- or L-NAME- treated preparations. Pnz or 4-DAMP alone had no effect on PE- induced contraction in all the preparations but in the presence of ACh Pnz or 4-DAMP con cent ration- dependently reversed ACh- induced relaxation in endothehummtact RTAs This was not observed in any of the saponin- or L-NAME-treated artenes It is concluded that endotheha! MI and Mi muscarimc receptors are involved in ACh- induced relaxation of the RTA.