Endothelium-dependent contraction induced by acetylcholine in isolated rat renal arteries.
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.
Nishimura
Y
Y
Department of Pharmacology, Kinki University School of Medicine, Osaka, Japan.
Usui
H
H
Kurahashi
K
K
Suzuki
A
A
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D018738:Hexamethonium / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D013729:Terpenes; C056566:S 145; D019335:Nitroarginine; D016718:Arachidonic Acid; D018738:Hexamethonium; D013928:Thromboxane A2; D001285:Atropine; C045749:SQ 29548; C049855:ONO 3708; D001120:Arginine; C045673:manoalide; D010741:Phospholipases A; D013930:Thromboxane-A Synthase; D011796:Quinacrine; D000109:Acetylcholine; D001241:Aspirin