CHARACTERIZATION OF THE MUSCARINIC RECEPTOR SUBTYPE MEDIATING VASODILATION IN THE RAT PERFUSED MESENTERIC VASCULAR BED PREPARATION

1 The nature of the muscarinic receptor subtype mediating endothelium-dependent vascular relaxation was investigated in the perfused mesenteric vascular bed preparation which is a model for resistance vessels. 2 After methoxamine-induced vasoconstriction the vessels were dilated with acetyl-beta-metacholine (MCh). 3 The potency of the M1-selective antagonist pirenzepine, the M2-selective antagonists AF-DX 116 and AQ-RA 741, the M3-selective antagonists 4-DAMP and p-FHHSiD to block the MCh-induced vasodilation was quantified by means of pA2-values. Atropine was used for comparison. 4 The rank order of potency for the various muscarinic receptor antagonists appears to be: atropine>4-DAMP>p-FHHSiD>pirenzepine>AQ-RA 741 >AF-DX 116 which is similar to findings in conduit arteries. 5 The high potency of the M3-selective antagonists 4-DAMP and p-FHHSID and the low potency of the M1- and M2-selective antagonists suggest a major role Of M3-receptors in the cholinergic vasodilatation in the perfused mesenteric vascular bed.