title: Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol.
abstract: Previous work has shown that the endogenous cystathionine gamma-synthase (CSE)/hydrogen sulfide (H(2)S) pathway participates in the regulation of cardiac contraction. We hypothesized that the pathway might participate in the pathophysiological regulation of ischemic heart disease. Isoproterenol injection of rat hearts induced a myocardial ischemic injury model, with reduced myocardial and plasma H(2)S levels, decreased CSE activity, and upregulated CSE gene expression. Exogenous administration of the H(2)S donor NaHS reduced the mortality rate; increased left-ventricular pressure development and left-ventricular-end systolic pressure; and decreased left-ventricular-end diastolic pressure (LVEDP) and subendocardial necrosis, capillary dilatation, leukocytic infiltration, fibroblast swelling, and fibroblastic hyperplasia. As well, production of lipid peroxidation, including myocardial malondialdehyde (MDA), and plasma MDA and conjugated diene, was reduced. Oxidative stress injury is an important mechanism of isoproterenol-induced myocardial injury. In vitro experiments revealed that NaHS might antagonize myocyte MDA production by oxygen-free radicals and that NaHS directly scavenged hydrogen peroxide and superoxide anions. Our results suggest that the endogenous CSE/H(2)S pathway contributes to the pathogenesis of isoproterenol-induced myocardial injury. Administration of exogenous H(2)S effectively protects myocytes and contractile activity, at least by its direct scavenging of oxygen-free radicals and reducing the accumulation of lipid peroxidations.
authors.affiliation: Department of Physiology, Peking University Health Science Center, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.forename: Lin
authors.initials: L
authors.lastname: Chang
authors.forename: Chunshui
authors.initials: C
authors.lastname: Pan
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Qi
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Pang
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
mesh_terms: D000475:Alkenes / Q000097:blood; D000818:Animals; D019757:Carbon-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology
chemical_list: D000475:Alkenes; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D013440:Sulfides; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; C022696:O-succinylhomoserine (thiol)-lyase; D003402:Creatine Kinase; D019757:Carbon-Oxygen Lyases; C025451:sodium bisulfide; D007545:Isoproterenol; D006862:Hydrogen Sulfide