sq-29548 and manoalide

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 microM) caused a transient contraction in endothelium-intact arteries in a concentration-dependent manner. The contraction induced by acetylcholine (10 microM) was enhanced by pretreatment with NG-nitro-L-arginine (100 microM), a nitric oxide synthase inhibitor, and was abolished by mechanical removal of the endothelium. Atropine (0.1 microM), quinacrine (1 and 3 microM), manoalide (0.1 and 1 microM), aspirin (1 and 10 microM), indomethacin (30 and 300 nM), ONO-3708 (9,11-dimethyl-methane-11,12-methano-13,14-dihydro-13-aza-14- oxo-15(beta)-cyclophenyl-omega-pentenor-thromboxane A2 L-arginine salt) (10 nM), S-1452 (calcium (5Z)-1R,2S,3S,4S-7-[3-phenylsulphonyl-aminobicyclo[2.2.1]hep t-2yl]-5- heptenoate hydrate) (3 nM) and SQ29,548 ([1S- [1 alpha,2 beta(5Z),3 beta,4 alpha]]-7-[3-[[2-[(phenylamino) carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoi++ + c acid) (3 and 10 nM), but not hexamethonium (1 microM), OKY-046 (sodium (E)-3-[4-(1- imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate) (100 microM) and CS-518 (sodium 2-(1-imidazolylmethyl)-4,5- dihydrobenzo[b]thiophene-6-carboxylate) (10 microM) significantly attenuated the acetylcholine (10 microM)-induced endothelium-dependent contractions in renal arteries pretreated with NG-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.

Topics: Acetylcholine; Animals; Arachidonic Acid; Arginine; Aspirin; Atropine; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Dose-Response Relationship, Drug; Endothelium, Vascular; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Hexamethonium; Hydrazines; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nitroarginine; Phospholipases A; Quinacrine; Rats; Rats, Inbred WKY; Receptors, Prostaglandin; Renal Artery; Terpenes; Thromboxane A2; Thromboxane-A Synthase