CHARACTERIZATION OF MUSCARINIC RECEPTOR SUBTYPE MEDIATING CONTRACTIONAND RELAXATION IN EQUINE CORONARY-ARTERY IN-VITRO

In coronary arterial rings isolated from horses, 10(-8)-10(-6) mol/l a cetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment wit h L-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower con centrations of ACh (10(-14)-10(-8) mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced cont ractions in the coronary rings without endothelium were competitively inhibited by:each muscarinic subtype selective antagonist in the follo wing order of potency: 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine greater-than-or-equal-to parafluoro-hexahydros iladiphenidol (pFHHSiD) > methoctramine. ACh-induced relaxation in the rings with endothelium was inhibited by LNAG or MB, and by each selec tive antagonist in the following order of potency: 4-DAMP > pFBHSID > pirenzepine > methoctramine. These results suggest that the ACh-induce d contraction and relaxation in equine coronary arteries are mediated mainly by an M3-receptor located on the smooth muscle cells and endoth elial cells, respectively, and that the stimulation of the M3-receptor on the endothelial cells liberates nitric oxide.