Abstract
We here assessed the effects of 3-[2-[4-(3-chloro-2-methylphenyl)-1- piperazinyl] ethyl]-5,6-dimethoxy-1-(4-imidazorylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, on infarct size in the rat heart subjected to ischemia /reperfusion. Rats were subjected to a 30-min coronary occlusion followed by a 24-h reperfusion. DY-9760e was intravenously infused for 20 min, starting at 20 min after coronary occlusion. Treatment with DY-9760e (10 mg/kg) significantly reduced the infarct size in the risk area assessed by Evans Blue/TTC (triphenyltetrazolium chloride) staining. DY-9760e treatment also ameliorated contractile dysfunction of the left ventricle 72 h after reperfusion. DY-9760e significantly inhibited fodrin breakdown and caspase-3 activation. The inhibitory effect of DY-9760e on the fodrin breakdown was prominent in the rim rather than in the center of the risk area. DY-9760e also blocked protein tyrosine nitration associated with infarction. These results suggest that the cardioprotective effect of DY-9760e involved inhibition of calpain/caspase activation and protein tyrosine nitration.
Original language | English |
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Pages (from-to) | 142-150 |
Number of pages | 9 |
Journal | Journal of Pharmacological Sciences |
Volume | 98 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2005 Jun |
Keywords
- Calmodulin antagonist
- Calpain
- Cardiomyocyte
- Caspase-3
- Coronary occlusion
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology