title: Hydrogen sulfide prevents heart failure development via inhibition of renin release from mast cells in isoproterenol-treated rats.
abstract: OBJECTIVE
  Cardiac local renin-angiotensin system plays an important role in the development of heart failure and left ventricular (LV) remodeling. We previously reported that hydrogen sulfide (H2S), an endogenous gaseous mediator, regulates renin synthesis and release in juxtaglomerular cells. The present study was designed to investigate whether H2S can protect against isoproterenol (ISO)-induced heart failure via inhibition of local renin activity in rat hearts.
  
  
  RESULTS
  In the present study, we found that an injection of ISO (150 mg/kg) significantly increased plasma lactate dehydrogenase level and hypertrophy index and impaired LV end diastolic pressure. Treatment with NaHS (an H2S donor, 0.056 mg/kg, daily) 3 days before and 2 weeks after the ISO injection attenuated the development of heart failure. Histological staining showed that NaHS decreased ISO-induced collagen deposition. Moreover, NaHS treatment reversed ISO-induced renin elevation in both plasma and LVs. Immunostaining analysis indicated that renin expression co-localized with mast cells in the ventricular tissues. Mast cell counts showed that NaHS treatment decreased the number of degranulated mast cells in cardiac tissue due to down-regulation of leukotriene A4 hydrolase protein expression and leukotriene B4 level. In addition, NaHS treatment also inhibited forskolin-induced renin degranulation from HMC-1.1 mast cells by lowering intracellular cAMP level.
  
  
  METHODS
  This study provides evidence for a new pathway in H2S-induced cardioprotection against heart failure development.
  
  
  CONCLUSIONS
  For the first time, we demonstrated that H2S might protect heart during heart failure by suppression of local renin level through inhibition of both mast cell infiltration and renin degranulation.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore, Singapore .
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Xie
authors.forename: Fei
authors.initials: F
authors.lastname: Hua
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Jun Hong
authors.initials: JH
authors.lastname: Gao
authors.forename: Yung-Hua
authors.initials: YH
authors.lastname: Koh
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006862:Hydrogen Sulfide / Q000494:pharmacology* / Q000627:therapeutic use; D007545:Isoproterenol; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007975:Leukotriene B4 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000378:metabolism*; D017725:Ventricular Pressure
chemical_list: D002316:Cardiotonic Agents; D007975:Leukotriene B4; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D004851:Epoxide Hydrolases; D012083:Renin; D007545:Isoproterenol; C043134:leukotriene A4 hydrolase; D006862:Hydrogen Sulfide