Signal Transduction in the Cardioprotective Effect of Alcohol

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Epidemiologic studies have shown that light to moderate ethanol use is associated with a protective effect against fatal coronary artery disease. We showed that the cardioprotective effect of ethanol requires adenosine A1 receptor activation at the time of ischemia, like experimental ischemic preconditioning (PC). We investigated the potential downstream mediators of this protection, compared with PC.[1] Is ethanol's protective effect abolished by PKC inhibitor, chelerythrine? 2. Are α,δandεprotein kinase C(PKC) translocated in myocytes from ethanol exposed hearts versus controls, like PC? (1) The improved contradtile recovery by ethanol was abolished by chelerythrine. (2) Western blot analysis and immunofluorescence localization demonstrate that regular ethanol consumption causes sustained translocation of εPKC, but not δor αPKC. This same enzyme is directly implicated in PC's protection against ischemia-reperfusion injury. These findings suggest (i) that regular ethanol consumption induces long-term cardioprotection through sustained translocation of εPKC and (ii) that PKC activity is necessary at the time of ischemia to mediate ethanol's protective effect.[2] Is the cardioprotective effect mediated by species-specific signaling like PC? Adenosine receptor blockade abolished ethanol's protection in guinea pig but not rat hearts. By contrast, α1-adrenergic blockade abolished ethanol's protection in rat but not guinea pig hearts. These finding are similar to PC.[3] Is phospholipase C(PLC) involved in the cardioprotective effect of ethanol? PLC blockade abolished ethanol's protection in guinea pig hearts, similar to PC.These results suggest that the cardioprotective effect of alcohol can be used for clinical application as a chronic ischemic preconditioning.