Characterization of the muscarinic receptor subtype mediating vasodilation in the rat perfused mesenteric vascular bed preparation

Abstract

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.