CHARACTERIZATION OF MUSCARINIC RECEPTORS MEDIATING VASODILATION IN RAT PERFUSED KIDNEY

The muscarinic receptor mediating vasodilation of resistance vessels i n the rat isolate , constant-pressure per (preconstriction by 10(-7) M cirazoline) was characterized by subtype-preferring agonists and sele ctive antagonists. The agonists produced vasodilation with the followi ng rank order of potency: arecaidine propargyl ester (APE) > 5-methylf urtrethonium = methacholine = oxotremorine > (S)-aceclidine > arecaidi ne 2-butyne-1,4-diyl bisester > 4-Cl-McN-A-343 = (R)-nipecotic acid et hyl ester = N-ethyl-guvacine propargyl ester approximately (R)-aceclid ine = (S)-nipecotic acid ethyl ester > McN-A-343. Agonist-induced vaso dilation disappeared after destruction of the endothelium with deterge nt. Highly significant correlations of agonist potencies for vasodilat ion were found between rat kidney and guinea-pig ileum submucosal arte rioles as well as agonist potencies at smooth muscle muscarinic M rece ptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > (R)-hexahy dro-difenidol approximately hexahydro-sila-difenidol > pirenzepine app roximately p-fluorohexahydro-sila-difenidol approximately himbacine ap proximately AF-DX 384 approximately AQ-RA 741 > (S)-hexahydro-difenido l) to attenuate vasodilation to APE in rat kidney, correlated signific antly with affinities at M3 receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M1 a nd M2 receptors in rabbit vas deferens. The agonist and antagonist pot encies suggest that vasodilation elicited by muscarinic stimuli in end othelium-intact rat renal vasculature is mediated by functional muscar inic M3 receptors.