PT  - JOURNAL ARTICLE
AU  - Reiko Takahashi
AU  - Yasuhisa Shimazaki
AU  - Masao Endoh
TI  - Decrease in Ca<sup>2+</sup>-Sensitizing Effect of UD-CG 212 Cl, a Metabolite of Pimobendan, under Acidotic Condition in Canine Ventricular Myocardium
DP  - 2001 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1060--1066
VI  - 298
IP  - 3
4099  - http://jpet.aspetjournals.org/content/298/3/1060.short
4100  - http://jpet.aspetjournals.org/content/298/3/1060.full
SO  - J Pharmacol Exp Ther2001 Sep 01; 298
AB  - We studied the influence of acidosis on the 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, in canine ventricular trabeculae loaded with aequorin. The positive inotropic effect of UD-CG 212 Cl was markedly suppressed under acidotic conditions. The maximal contractile response to UD-CG 212 Cl was attained at 10−5 M in the control condition at pH 7.4, but was not achieved even at 10−4 M during acidosis. The maximal inotropic effect of UD-CG 212 Cl was 18% of the maximal response to isoproterenol (ISOmax) in association with an increase in Ca2+ transients of 7% of ISOmax in the control, while they are 8 and 6% of ISOmax under acidosis, respectively. Acidosis abolished the increase in myofilament Ca2+ sensitivity induced by UD-CG 212 Cl, whereas the increase in Ca2+ transients induced by the compound was not affected by acidosis. In conclusion, UD-CG 212 Cl elicited a positive inotropic effect even under acidosis, however, UD-CG 212 Cl was much less effective as a cardiotonic agent under acidosis mainly due to a decrease in the Ca2+-sensitizing effect under acidotic condition. The American Society for Pharmacology and Experimental Therapeutics