title: Hydrogen sulfide attenuates cardiac dysfunction in a rat model of heart failure: a mechanism through cardiac mitochondrial protection.
abstract: HF (heart failure) after MI (myocardial infarction) is a major cause of morbidity and mortality worldwide. Recent studies have shown that hydrogen sulfide (H2S) has cardioprotective effects. Hence, we aimed to elucidate the potential effects of H2S on HF after MI in rats. The HF model after MI was made by ligating the left anterior descending coronary artery. HF groups and sham-operated groups of rats were treated with vehicle, sodium hydrosulfide (NaHS) or PAG (propagylglycine). Equal volumes of saline, 3.136 mg · kg-1 · day-1 NaHS or 37.5 mg · kg-1 · day-1 PAG, were intraperitoneally injected into rats for 6 weeks after operation. Survival, lung-to-body weight ratio and left ventricular haemodynamic parameters were measured. The protein and gene expression of Bcl-2, Bax, caspase 3 and cytochrome c were analysed by Western blotting and RT-PCR (reverse transcription-PCR). TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) and EM (electron microscopy) were used to examine apoptosis of heart tissues. NaHS was found to improve the survival and lower the lung-to-body weight ratio. It increased the LVSP (left ventricular systolic pressure) and the maximum rate of pressure and decreased LVEDP (left ventricular end-diastolic pressure). Furthermore, NaHS promoted Bcl-2 protein and mRNA expression and demoted Bax, caspase 3 protein and mRNA expression in HF rats. We also showed that NaHS decreased the leakage of cytochrome c protein from the mitochondria to the cytoplasm. Histological observation by TUNEL and EM proved that NaHS inhibited cardiac apoptosis in HF hearts and improved mitochondrial derangements, but that PAG aggravated those indices. Hence, H2S has protective effects in HF rats.
authors.affiliation: Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D019254:Genes, bcl-2; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006862:Hydrogen Sulfide / Q000097:blood*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D013440:Sulfides / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D024101:Mitochondrial Proteins; D013440:Sulfides; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; C025451:sodium bisulfide; D006862:Hydrogen Sulfide
references.citation: Biochem Biophys Res Commun. 2004 Jan 9;313(2):362-8
references.pmid: 14684169
references.citation: Can J Physiol Pharmacol. 2003 Sep;81(9):848-53
references.pmid: 14614520
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8144-9
references.pmid: 10393962
references.citation: J Appl Physiol (1985). 2007 Jan;102(1):261-8
references.pmid: 17038495
references.citation: J Thorac Cardiovasc Surg. 2003 Jun;125(6):1461-9
references.pmid: 12830068
references.citation: J Clin Invest. 2005 Mar;115(3):565-71
references.pmid: 15765138
references.citation: J Neurochem. 2004 Aug;90(3):765-8
references.pmid: 15255956
references.citation: Circulation. 1997 Mar 4;95(5):1314-9
references.pmid: 9054865
references.citation: Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Feb 18;35(1):102
references.pmid: 12920821
references.citation: Circ Res. 1996 Nov;79(5):949-56
references.pmid: 8888687
references.citation: Acta Pharmacol Sin. 2007 Nov;28(11):1709-16
references.pmid: 17959020
references.citation: Biochem Biophys Res Commun. 1997 Aug 28;237(3):527-31
references.pmid: 9299397
references.citation: Am J Physiol Heart Circ Physiol. 2003 Feb;284(2):H456-63
references.pmid: 12414449
references.citation: FASEB J. 2005 Jul;19(9):1196-8
references.pmid: 15863703
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15560-5
references.pmid: 17878306
references.citation: J Heart Lung Transplant. 2002 Feb;21(2):189-203
references.pmid: 11834347
references.citation: J Appl Physiol (1985). 2003 Feb;94(2):752-63
references.pmid: 12531914
references.citation: Annu Rev Pharmacol Toxicol. 1992;32:109-34
references.pmid: 1605565
references.citation: Amino Acids. 2004 Jun;26(3):243-54
references.pmid: 15221504
references.citation: Biochem Biophys Res Commun. 2004 Jun 4;318(3):756-63
references.pmid: 15144903
references.citation: Circulation. 2000 Aug 22;102(8):915-20
references.pmid: 10952962
references.citation: Heart Fail Rev. 2008 Jun;13(2):111-9
references.pmid: 18080749
references.citation: Circ Res. 2004 Nov 12;95(10):957-70
references.pmid: 15539639
references.citation: J Mol Cell Cardiol. 2005 Jan;38(1):47-62
references.pmid: 15623421
references.citation: Dis Model Mech. 2010 Mar-Apr;3(3-4):138-43
references.pmid: 20212081
references.citation: Circulation. 2002 Sep 24;106(12 Suppl 1):I212-7
references.pmid: 12354736
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6252-6
references.pmid: 11972044
references.citation: J Clin Invest. 2003 May;111(10):1497-504
references.pmid: 12750399
references.citation: Ann Intern Med. 2005 Jan 18;142(2):132-45
references.pmid: 15657162
references.citation: Circ Res. 2004 Jun 25;94(12):1543-53
references.pmid: 15217919
references.citation: FASEB J. 2002 Nov;16(13):1792-8
references.pmid: 12409322
references.citation: Mol Neurobiol. 2002 Aug;26(1):13-9
references.pmid: 12392053
references.citation: FASEB J. 2006 Oct;20(12):2118-20
references.pmid: 16912151
references.citation: Biol Pharm Bull. 2009 Aug;32(8):1406-10
references.pmid: 19652381
references.citation: Br J Pharmacol. 2004 Dec;143(7):881-9
references.pmid: 15504752
references.citation: Life Sci. 2003 Aug 1;73(11):1413-26
references.pmid: 12850502
references.citation: J Renin Angiotensin Aldosterone Syst. 2000 Sep;1(3):257-62
references.pmid: 11881034