Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning.
The present study aimed to investigate the role of hydrogen sulphide (H2S) in the cardioprotection induced by ischemic postconditioning and to examine the underlying mechanisms. Cardiodynamics and myocardial infarction were measured in isolated rat hearts. Postconditioning with six episodes of 10-s ischemia (IPostC) significantly improved cardiodynamic function, which was attenuated by the blockade of endogenous H2S production with d-l-propargylglycine. Moreover, IPostC significantly stimulated H2S synthesis enzyme activity during the early period of reperfusion. However, d-l-propargylglycine only attenuated the IPostC-induced activation of PKC-alpha and PKC-epsilon but not that of PKC-delta, Akt, and endothelial nitric oxide synthase (eNOS). These data suggest that endogenous H2S contributes partially to the cardioprotection of IPostC via stimulating PKC-alpha and PKC-epsilon. Postconditioning with six episodes of a 10-s infusion of NaHS (SPostC) or 2 min continuous NaHS infusion (SPostC2) stimulated activities of Akt and PKC, improved the cardiodynamic performances, and reduced myocardial infarct size. The blockade of Akt with LY-294002 (15 microM) or PKC with chelerythrine (10 microM) abolished the cardioprotection induced by H2S postconditioning. SPostC2, but not SPostC, also additionally stimulated eNOS. We conclude that endogenous H2S contributes to IPostC-induced cardioprotection. H2S postconditioning confers the protective effects against ischemia-reperfusion injury through the activation of Akt, PKC, and eNOS pathways.
Yong
Qian Chen
QC
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
Lee
Shiau Wei
SW
Foo
Chun Shin
CS
Neo
Kay Li
KL
Chen
Xin
X
Bian
Jin-Song
JS
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004562:Electrocardiography; D004789:Enzyme Activation; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006331:Heart Diseases / Q000517:prevention & control*; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D000480:Alkynes; D019138:Antibodies, Blocking; D002867:Chromones; D007074:Immunoglobulin G; D007527:Isoenzymes; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C009055:propargylglycine; D052250:Nitric Oxide Synthase Type III; D051058:Oncogene Protein v-akt; D011493:Protein Kinase C; D005998:Glycine; D004121:Dimethyl Sulfoxide; D006862:Hydrogen Sulfide