Increase in Myofibrillar Ca2+ Sensitivity Induced by UD-CG 212 Cl, an Active Metabolite of Pimobendan, in Canine Ventricular Myocardium
Department of Pharmacology, Yamagata University School of Medicine, Japan. Journal of Cardiovascular Pharmacology
(Impact Factor: 2.14).
03/2001; 37(2):209-18. DOI: 10.1097/00005344-200102000-00008
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.
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