Endothelium-dependent contraction induced by acetylcholine in isolated rat renal arteries

Abstract

We investigated whether or not acetylcholine elicited an endothelium-dependent contraction and whether an arachidonic acid metabolite was involved in the acetylcholine-induced contraction in ring preparations of rat renal arteries. Acetylcholine (0.1–100 μM) caused a transient contraction in endothelium-intact arteries in a concentration-dependent manner. The contraction induced by acetylcholine (10 μM) was enhanced by pretreatment with N G-nitro- l-arginine (100 μM), a nitric oxide synthase inhibitor, and was abolished by mechanical removal of the endothelium. Atropine (0.1 μM), quinacrine (1 and 3 μM), manoalide (0.1 and 1 μM), aspirin (1 and 10 μM), indomethacin (30 and 300 nM), ONO-3708 (9,11-dimethyl-methane-11,12-methano-13,14-dihydro-13-aza-14-oxo-15(β)-cyclophenyl-ω-pentenor-thromboxane A 2 l-arginine salt) (10 nM), S-1452 (calcium (5 Z)-1 R,2 S,3 S,4 S-7-[3-phenylsulphonyl-aminobicyclo[2.2.1]hept-2yl]-5-heptenoate hydrate) (3 nM) and SQ29,548 ([1 S-[1α,2β(5 Z),3β,4α]]-7-[3-[[2-[(phenylamino) carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) (3 and 10 nM), but not hexamethonium (1 μM), OKY-046 (sodium ( E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate) (100 μM) and CS-518 (sodium 2-(1-imidazolylmethyl)-4,5-dihydrobenzo[ b]thiophene-6-carboxylate) (10 μM) significantly attenuated the acetylcholine (10 μM)-induced endothelium-dependent contractions in renal arteries pretreated with N G-nitro- l-arginine. These findings suggest that acetylcholine causes endothelium-dependent contraction by stimulation of muscarinic receptors in rat renal arteries, and that an arachidonic acid metabolite(s) of the cyclooxygenase pathway is involved in this endothelium-dependent contraction.