Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes.
Endogenous H(2)S is synthesized mainly by cystathionine gamma-lyase in the heart. The present study investigated the role of H(2)S in cardioprotection induced by ischemic preconditioning. We have examined the effect of endogenous H(2)S and exogenous application of NaHS (H(2)S donor) on cardiac rhythm in the isolated rat heart subjected to low-flow ischemia insults as well as cell viability and function in isolated myocytes exposed to simulated ischemia solution. Preconditioning with NaHS (SP) or ischemia (IP) for three cycles (3 min each cycle separated by 5 min of recovery) significantly decreased the duration and severity of ischemia/reperfusion-induced arrhythmias in the isolated heart while increasing cell viability and the amplitude of electrically induced calcium transients after ischemia/reperfusion in cardiac myocytes. Both IP and SP also significantly attenuated the decreased H(2)S production during ischemia. Moreover, decreasing endogenous H(2)S production significantly attenuated the protective effect of IP in both the isolated heart and isolated cardiac myocytes. Blockade of protein kinase C with chelerythrine or bisindolylmaleimide I as well as ATP-sensitive K(+) (K(ATP)) channel with glibenclamide (a nonselective K(ATP) blocker) and HMR-1098 (1-[[5-[2-(5-Chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea) (a sarcolemmal K(ATP) channel blocker) reversed the cardioprotection induced by SP or IP. However, blockade of mitochondrial K(ATP) channels with 5-hydroxydecanoic acid had no effect on the cardioprotection of SP, suggesting that, unlike the mechanism involved in IP, mitochondrial K(ATP) channels most probably do not play a major role in the cardioprotection of SP. Our findings suggest that endogenous H(2)S contributes to cardioprotection induced by IP, which effect may involve protein kinase C and sarcolemmal K(ATP) channels.
Bian
Jin-Song
JS
Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, Singapore.
Yong
Qian Chen
QC
Pan
Ting-Ting
TT
Feng
Zhan-Ning
ZN
Ali
Muhammed Yusuf
MY
Zhou
Shufeng
S
Moore
Philip Keith
PK
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology
D002316:Cardiotonic Agents; D013440:Sulfides; C025451:sodium bisulfide; D002118:Calcium; D006862:Hydrogen Sulfide