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.
Hendriks
M G
MG
Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
Pfaffendorf
M
M
Van Zwieten
P A
PA
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology*; D016210:Methacholine Chloride / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001570:Benzodiazepinones; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; C058297:4-fluorohexahydrosiladifenidol; C069054:AQ-RA 741; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C048593:otenzepad