Decrease in Ca(2+)-sensitizing effect of UD-CG 212 Cl, a metabolite of pimobendan, under acidotic condition in canine ventricular myocardium.

Content Provider	Semantic Scholar
Author	Takahashi, Ryo Shimazaki, Yukio Endoh, Masao
Copyright Year	2001
Abstract	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 (ISO(max)) in association with an increase in Ca(2+) transients of 7% of ISO(max) in the control, while they are 8 and 6% of ISO(max) under acidosis, respectively. Acidosis abolished the increase in myofilament Ca(2+) sensitivity induced by UD-CG 212 Cl, whereas the increase in Ca(2+) 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 Ca(2+)-sensitizing effect under acidotic condition.
File Format	PDF HTM / HTML
PubMed reference number	11504803
Journal	Medline
Volume Number	298
Issue Number	3
Alternate Webpage(s)	http://jpet.aspetjournals.org/content/jpet/298/3/1060.full.pdf
Journal	The Journal of pharmacology and experimental therapeutics
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article