Journal
PHARMACOLOGY
Volume 82, Issue 3, Pages 201-213Publisher
KARGER
DOI: 10.1159/000156486
Keywords
volume overload; arteriovenous fistula; sodium thiosulfate; collagen; matrix metalloproteinase; adenylate cyclase; hydrogen sulfide; cystathionine; beta-synthase; cystathionine gamma-lyase
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Funding
- NIH [HL-71010, HL-88012, HL-74185, NS-51568]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL074185, R01HL088012, R01HL071010] Funding Source: NIH RePORTER
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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 (H2S), cystathionine-gamma-lyase (CSE) expression was attenuated in AVF mice with no changes in cystathionine-beta-synthase (CBS) expression. In addition, reduced production of H2S in AVF ventricular tissue was normalized with STS supplementation. Moreover, cardiac tissues were more responsive to H2S 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 H2S generation. Copyright (C) 2008 S. Karger AG, Basel.
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