title: Increase in myofibrillar Ca2+ sensitivity induced by UD-CG 212 Cl, an active metabolite of pimobendan, in canine ventricular myocardium.
abstract: We performed experiments in canine ventricular trabeculae loaded with aequorin to elucidate the mechanism of positive inotropic effect of UD-CG 212 Cl (4,5-dihydro-6-[2-(4-hydroxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3(2H)-pyridazinone), an active metabolite of pimobendan. The maximum response to UD-CG 212 Cl achieved at 10(-5) M was 18% of ISOmax and it was associated with an increase in Ca2+ transients of 7% of ISOmax. For a given increase in force, the increase in Ca2+ transients induced by UD-CG 212 Cl was less than that induced by elevation of [Ca2+]o. The positive inotropic effect of UD-CG 212 Cl was not associated with an impairment of relaxation and it was abolished by carbachol. In conclusion, UD-CG 212 Cl has a positive inotropic effect partly due to an increase in myofibrillar Ca2+ sensitivity that is exerted via cross talk with a signal transduction pathway that involves cAMP.
authors.affiliation: Department of Pharmacology, Yamagata University School of Medicine, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.forename: M
authors.initials: M
authors.lastname: Endoh
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009210:Myofibrils / Q000378:metabolism*; D011724:Pyridazines / Q000378:metabolism* / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; C047936:UD CG 212 Cl; D002217:Carbachol; D002118:Calcium