Acetylcholine-induced positive inotropy mediated by prostaglandin released from endocardial endothelium in mouse left atrium.
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.
Tanaka
H
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan. htanaka@phar.toho-u.ac.jp
Nishimaru
K
K
Kobayashi
M
M
Matsuda
T
T
Tanaka
Y
Y
Shigenobu
K
K
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*
D010120:Oxytocics; D011453:Prostaglandins; D014665:Vasodilator Agents; D015237:Dinoprost; D000109:Acetylcholine