title: Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway.
abstract: OBJECTIVE
  H2S is known to confer cardioprotection; however, the pathways mediating its effects in vivo remain incompletely understood. The purpose of the present study is to evaluate the contribution of cGMP-regulated pathways in the infarct-limiting effect of H2S in vivo.
  
  
  RESULTS
  Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide (NaHS, an agent that generates H2S) increased cardiac cGMP and reduced the infarct size. The cGMP-dependent protein kinase (PKG)-I inhibitor DT2 abrogated the protective effect of NaHS, whereas the control peptide TAT or l-nitroarginine methyl ester (l-NAME) did not alter the effect of NaHS. Moreover, the KATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial KATP did not modify the NaHS response. NaHS enhanced phosphorylation of phospholamban (PLN), in a PKG-dependent manner. To further investigate the role of PLN in H2S-mediated cardioprotection, wild-type and PLN KO mice underwent I/R. NaHS did not exert cardioprotection in PLN KO mice. Unlike what was observed in rabbits, genetic or pharmacological inhibition of eNOS abolished the infarct-limiting effect of NaHS in mice.
  
  
  CONCLUSIONS
  Our findings demonstrate (i) that administration of NaHS induces cardioprotection via a cGMP/PKG/PLN pathway and (ii) contribution of nitric oxide to the H2S response is species-specific.
authors: Faculty of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771, Greece.
authors: Sofia-Iris
authors: SI
authors: Bibli
authors: Faculty of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771, Greece jandread@pharm.uoa.gr apapapet@pharm.uoa.gr.
authors: Ioanna
authors: I
authors: Andreadou
authors: Faculty of Medicine, First Department of Critical Care and Pulmonary Services, Evangelismos Hospital, University of Athens, Athens, Greece.
authors: Athanasia
authors: A
authors: Chatzianastasiou
authors: Molecular Biology Department, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Christos
authors: C
authors: Tzimas
authors: Molecular Biology Department, Biomedical Research Foundation of the Academy of Athens, Athens, Greece Department of Pharmacology, Faculty of Medicine, University of Athens, Athens, Greece.
authors: Despina
authors: D
authors: Sanoudou
authors: Molecular Biology Department, Biomedical Research Foundation of the Academy of Athens, Athens, Greece Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
authors: Evangelia
authors: E
authors: Kranias
authors: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Department of Molecular Biomedical Research, VIB, Ghent, Belgium.
authors: Peter
authors: P
authors: Brouckaert
authors: Department of Anesthesiology University of Texas Medical Branch, Galveston, TX, USA Shriners Burns Hospital for Children, Galveston, TX, USA.
authors: Ciro
authors: C
authors: Coletta
authors: Department of Anesthesiology University of Texas Medical Branch, Galveston, TX, USA Shriners Burns Hospital for Children, Galveston, TX, USA.
authors: Csaba
authors: C
authors: Szabo
authors: Faculty of Medicine, Second Department of Cardiology, Attikon University Hospital, University of Athens, Athens, Greece.
authors: Dimitrios Th
authors: DT
authors: Kremastinos
authors: Faculty of Medicine, Second Department of Cardiology, Attikon University Hospital, University of Athens, Athens, Greece.
authors: Efstathios K
authors: EK
authors: Iliodromitis
authors: Faculty of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771, Greece Molecular Biology Department, Biomedical Research Foundation of the Academy of Athens, Athens, Greece jandread@pharm.uoa.gr apapapet@pharm.uoa.gr.
authors: Andreas
authors: A
authors: Papapetropoulos
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects*; D013045:Species Specificity; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D006862:Hydrogen Sulfide; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D047428:Protein Kinase Inhibitors; D013440:Sulfides; D000099211:Phospholamban; C496315:Nos3 protein, mouse; C025451:sodium bisulfide
keywords: H2S; Ischaemia; Phospholamban; Postconditioning; cGMP