Alcohol consumption reduces ischemia-reperfusion injury by species-specific signaling in guinea pigs and rats.
We recently discovered that regular alcohol consumption reduces ischemia-reperfusion injury to the same degree as ischemic preconditioning in guinea pig hearts. Ischemic preconditioning, like this cardioprotective effect of alcohol, is mediated by adenosine signaling in guinea pigs. In rats, ischemic preconditioning may be mediated predominantly by alpha1-adrenergic signaling. To be certain that this protective effect of alcohol is a general biological response, we searched for alcohol's cardioprotection in rat and identified a potential signaling mechanism. Hearts isolated from alcohol-fed guinea pigs and rats were subjected to ischemia-reperfusion. Hearts from alcohol-fed animals showed greater recovery of left ventricular developed pressure than controls (guinea pigs, 46 vs. 29%; rats, 50 vs. 31%) and decreased myocyte necrosis assessed by creatine kinase release (guinea pigs, 204 +/- 42 vs. 440 +/- 70 U . ml-1 . g dry wt-1; rats 158 +/- 13 vs. 328 +/- 31 U . ml-1 . g dry wt-1). Adenosine receptor blockade [8-(p-sulfophenyl)theophylline] abolished alcohol's protection in guinea pig but not rat hearts. By contrast, alpha1-adrenergic blockade (prazosin) abolished alcohol's protection in rat but not guinea pig hearts. We conclude that regular alcohol consumption reduces ischemia-reperfusion injury and is mediated by species-specific signaling mechanisms. A major goal of cardiovascular research is to find a pharmacologically induced chronic state of preconditioning. Understanding the mechanisms of alcohol's cardioprotection against ischemia-reperfusion injury may aid in reaching this goal.
Department of Medicine (Cardiology), San Francisco General Hospital, University of California, San Francisco, California 94110, USA.
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D000428:Alcohol Drinking / Q000473:pathology / Q000503:physiopathology*; D000437:Alcoholism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000032:analysis; D003971:Diastole; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011224:Prazosin / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012016:Reference Values; D015398:Signal Transduction; D013045:Species Specificity; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D016277:Ventricular Function, Left
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D003402:Creatine Kinase; D011224:Prazosin