Document Detail


Cardioprotective role of sodium thiosulfate on chronic heart failure by modulating endogenous H2S generation.
MedLine Citation:
PMID:  18810244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Sodium thiosulfate (STS) has been shown to be an antioxidant and calcium solubilizer, but the possible role of STS in dysfunctional ventricles remains unknown. Here, we assessed the effects of STS in the failing heart. METHODS: Heart failure was created by an arteriovenous fistula (AVF). Mice were divided into 4 groups: sham, AVF, sham + STS, and AVF + STS. STS (3 mg/ml) was supplemented with drinking water for 6 weeks in the appropriate surgery groups after surgery. RESULTS: M-mode echocardiograms showed ventricular contractile dysfunction with reduced aortic blood flow in AVF mice, whereas STS treatment prevented the decline in cardiac function. Ventricular collagen, MMP-2 and -9, and TIMP-1 were robustly increased with a decreasing trend in adenylate cyclase VI expression; however, STS supplementation reversed these effects in AVF mice. Among 2 enzymes that produce endogenous hydrogen sulfide (H(2)S), cystathionine-gamma-lyase (CSE) expression was attenuated in AVF mice with no changes in cystathionine-beta-synthase (CBS) expression. In addition, reduced production of H(2)S in AVF ventricular tissue was normalized with STS supplementation. Moreover, cardiac tissues were more responsive to H(2)S when AVF mice were supplemented with STS compared to AVF alone. CONCLUSIONS: These results suggested that STS modulated cardiac dysfunction and the extracellular matrix, in part, by increasing ventricular H(2)S generation.
Authors:
Utpal Sen; Thomas P Vacek; William M Hughes; Munish Kumar; Karni S Moshal; Neetu Tyagi; Naira Metreveli; Melvin R Hayden; Suresh C Tyagi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-23
Journal Detail:
Title:  Pharmacology     Volume:  82     ISSN:  1423-0313     ISO Abbreviation:  Pharmacology     Publication Date:  2008  
Date Detail:
Created Date:  2008-10-14     Completed Date:  2009-01-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  201-13     Citation Subset:  IM    
Copyright Information:
Copyright 2008 S. Karger AG, Basel.
Affiliation:
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY 40202, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / genetics,  metabolism
Animals
Aorta / physiopathology
Arteriovenous Fistula
Cardiotonic Agents / pharmacology*
Chronic Disease
Collagen / drug effects,  metabolism
Cystathionine gamma-Lyase / drug effects,  metabolism
Echocardiography
Gene Expression Regulation, Enzymologic / drug effects
Heart Failure / drug therapy*,  physiopathology
Hydrogen Sulfide / metabolism*
Male
Matrix Metalloproteinase 2 / drug effects,  metabolism
Matrix Metalloproteinase 9 / drug effects,  metabolism
Mice
Mice, Inbred C57BL
Myocardial Contraction / drug effects
Thiosulfates / pharmacology*
Tissue Inhibitor of Metalloproteinase-1 / drug effects,  metabolism
Grant Support
ID/Acronym/Agency:
HL-71010/HL/NHLBI NIH HHS; HL-74185/HL/NHLBI NIH HHS; HL-88012/HL/NHLBI NIH HHS; NS-51568/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cardiotonic Agents; 0/Thiosulfates; 0/Tissue Inhibitor of Metalloproteinase-1; 7772-98-7/sodium thiosulfate; 7783-06-4/Hydrogen Sulfide; 9007-34-5/Collagen; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 4.4.1.1/Cystathionine gamma-Lyase; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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