title: Acetylcholine-induced positive inotropy mediated by prostaglandin released from endocardial endothelium in mouse left atrium.
abstract: The possible involvement of the endocardial endothelium in the positive inotropic response of the mouse left atrium to acetylcholine was examined pharmacologically. In mouse left atria, acetylcholine produced a biphasic inotropic response: a transient decrease in contractile force followed by a late increase. The positive response was not affected by the presence of phentolamine and propranolol, but was almost abolished by pretreatment of the preparation with 1% Triton X-100, which denudes the endocardium of its endothelium. Nordihydroguaiaretic acid, NG-nitro-L-arginine, BQ-123 and BQ-788 had no effect on the inotropic responses to acetylcholine, but indomethacin completely abolished the positive response. Prostaglandins and their analogues had a positive inotropic effect with a potency order PGF2alpha>PGD2>PGE2>U46619, whereas beraprost had no effect. Neither Triton X-100 pretreatment nor the presence of indomethacin affected the positive inotropic effect of PGF2alpha. Acetylcholine and PGF2alpha prolonged the action potential duration similarly. These results suggest that the acetylcholine-induced positive inotropic response in mouse left atria is mediated by prostaglandin released from the endocardial endothelium.
authors.affiliation: Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan. htanaka@phar.toho-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Nishimaru
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Shigenobu
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D015237:Dinoprost / Q000494:pharmacology; D004699:Endocardium / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010120:Oxytocics / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology*; D013268:Stimulation, Chemical; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010120:Oxytocics; D011453:Prostaglandins; D014665:Vasodilator Agents; D015237:Dinoprost; D000109:Acetylcholine