Investigation of the mechanism(s) of flavonol‐induced cardioprotection in rat isolated hearts (652.7)

Abstract

The synthetic flavonol 3’,4’‐dihydroxyflavonol (DiOHF) reduces myocardial ischaemia/reperfusion (I/R) injury however the mechanism of DiOHF‐induced cardioprotection remains to be elucidated. We tested the hypothesis that the DiOHF‐induced cardioprotection results from selectively inhibiting injurious kinases without affecting protective kinases. Langendorff‐perfused rat hearts were subjected to 20 min global ischaemia followed by 30 min reperfusion in the presence of DiOHF (10 µM) or its vehicle (0.5% dimethyl sulfoxide). Hearts treated with DiOHF showed improved post‐ischaemic cardiac function and lower lactate dehydrogenase (LDH) release compared to its vehicle. DiOHF treatment significantly reduced I/R‐induced increased phosphorylation of c‐Jun N‐terminal kinases (JNK), measured by Western blot, while I/R‐activated phosphorylation of p38 mitogen‐activated protein kinase, extracellular signal‐regulated kinases (ERK) 1/2 and signal transducer and activator of transcription 3 were not affected. In addition, the phosphorylation of the multifunctional enzyme, Ca2+/calmodulin‐dependent kinase II (CaMKII) was elevated in I/R and was reduced by DiOHF. These data suggest that DiOHF‐induced cardioprotection against I/R injury is mediated by inhibiting the phosphorylation of the injurious kinases JNK and CaMKII without affecting protective kinases.