During myocardial ischemia/reperfusion, lipid peroxidation leads to formation of toxic aldehydes that contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase type 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. This study tested whether reduced norepinephrine release in vitro may be part of the reason for improved function with ALDH2. Incubation of cardiac sympathetic nerve endings under conditions similar to ischemia (high acetaldehyde and hypoxia) caused increases in norepinephrine release. Selective activation of adenosine A1, A3, or histamine H3 receptors markedly inhibited both acetaldehyde and hypoxia-induced norepinephrine release. These effects were correlated with increased ALDH2 activity and were abolished by ALDH2 inhibition. These findings suggest the existence in sympathetic neurons of a protective pathway that could be activated by adenosine and histamine. In addition, this pathway encompasses the activation of ALDH2. Thus, the pharmacological activation of ALDH2 in cardiac sympathetic nerves may have protective effects by alleviating norepinephrine-induced arrhythmias that characterize ischemia/reperfusion.
See article at J Pharmacol Exp Ther 2012, 343:97–105.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics