title: Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes.
abstract: The possible role of hydrogen sulfide (H2S) in cardioprotection was investigated in isolated rat ventricular myocytes exposed to severe metabolic inhibition (MI) in glucose-free buffer containing 2-deoxy-D-glucose (2-DOG), an inhibitor of glycolysis. Pretreatment (30 min) with NaHS (a H2S donor) at concentrations of 10(-5) to 10(-4) mol/L caused a concentration related increase in cell viability and the ratio of rod-shaped cells. A time course study showed that NaHS-induced cardioprotection occurred in 2 time windows (approximately 1 h and 16-28 h). To observe whether endogenous H2S may be involved in the delayed cardioprotection response of IP, DL-propargylglycine (PAG) and beta-cyano-L-alanine (BCA; two inhibitors of H2S biosynthesis) were used. Both drugs significantly attenuated the cardioprotection produced by MI using cell viability, cellular injury index, and electrically-induced [Ca2+]i transients as end-points. These data suggest that endogenous H2S plays an important role in the cardioprotection following MI preconditioning. In an attempt to determine the mechanism of the cardioprotective effect of H2S, we examined the effect of blocking KATP channels with glibenclamide (a non-selective KATP channel blocker), 5-hydroxydecanoic acid (5-HD, a mitochondrial KATP blocker), and HMR-1098 (a sarcolemmal KATP blocker). The cardioprotective effects of NaHS were significantly attenuated by glibenclamide and HMR-1098 treatment but not by 5-HD. Inhibition of NO production with L-NG nitroarginine methyl ester (L-NAME) also attenuated the cardioprotection of NaHS. In conclusion, our findings provide the first evidence that H2S may protect the heart most probably by activating sarcolemmal KATP channels and/or provoking NO release and the cardioprotective effects of metabolic ischemic preconditioning is, at least partially, mediated by endogenous H2S.
authors.affiliation: Cardiovascular Research Group, Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore, 117597.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Pan
authors.forename: Zhan-Ning
authors.initials: ZN
authors.lastname: Feng
authors.forename: Shiau Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Philip Keith
authors.initials: PK
authors.lastname: Moore
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005905:Glyburide / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016276:Ventricular Function
chemical_list: D000480:Alkynes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D020011:Protective Agents; D009569:Nitric Oxide; C009055:propargylglycine; C004631:3-cyanoalanine; D000409:Alanine; D005905:Glyburide; D002118:Calcium; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester; D006862:Hydrogen Sulfide