Characterization of muscarinic receptors mediating vasodilation in rat perfused kidney

• Published in: European journal of pharmacology Vol. 238; no. 2-3; pp. 343 - 355
• Main Authors: ELTZE, M, ULLRICH, B, MUTSCHLER, E, MOSER, U, BUNGARDT, E, FRIEBE, T, GUBITZ, C, TACKE, R, LAMBRECHT, G
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 20.07.1993
• Subjects: Animals; Arterioles - drug effects; Arterioles - metabolism; Biological and medical sciences; Endothelium, Vascular - drug effects; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Ileum - drug effects; In Vitro Techniques; Intestinal Mucosa - blood supply; Intestinal Mucosa - drug effects; Kidney - blood supply; Kidney - drug effects; Male; Muscarinic Antagonists; Muscle, Smooth - drug effects; Parasympatholytics - pharmacology; Parasympathomimetics - metabolism; Parasympathomimetics - pharmacology; Perfusion; Rabbits; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Vas Deferens - drug effects; Vas Deferens - metabolism; Vascular Resistance - drug effects; Vasodilation - drug effects; Vertebrates: urinary system; Heart; Agonist; Rat; Arteriole; Rabbit; Smooth muscle; Kidney; Vasodilation; Guinea pig; Submucosa; Antagonist; M3 receptor; Atrium; Digestive system; Rodentia; Lagomorpha; Male genital system; Ileum; In vitro; Vas deferens; Vertebrata; Mammalia; Urinary system; Muscarinic receptor; Circulatory system; Comparative study
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(93)90866-G

The muscarinic receptor mediating vasodilation of resistance vessels in the rat isolated, constant-pressure perfused kidney (preconstriction by 10(-7) M cirazoline) was characterized by subtype-preferring agonists and selective antagonists. The agonists produced vasodilation with the following rank order of potency: arecaidine propargyl ester (APE) > 5-methylfurtrethonium = methacholine = oxotremorine > (S)-aceclidine > arecaidine 2-butyne-1,4-diyl bisester > 4-Cl-McN-A-343 = (R)-nipecotic acid ethyl ester = N-ethyl-guvacine propargyl ester approximately (R)-aceclidine = (S)-nipecotic acid ethyl ester > McN-A-343. Agonist-induced vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as well as agonist potencies at smooth muscle muscarinic M3 receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol approximately hexahydro-sila-difenidol > pirenzepine approximately p-fluoro-hexahydro-sila-difenidol approximately himbacine approximately AF-DX 384 approximately AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M3 receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M1 and M2 receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M3 receptors.