Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II‐induced hypertensive heart disease in rats

Abstract

BACKGROUND AND PURPOSEHypertension is an important mediator of cardiac damage and remodelling. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cardioprotective properties. However, it is not yet in clinical use. We, therefore, investigated the protective effects of sodium thiosulfate (STS), a clinically applicable H2S donor substance, in angiotensin II (Ang II)-induced hypertensive cardiac disease in rats. EXPERIMENTAL APPROACHMale Sprague Dawley rats were infused with Ang II (435 ng kg min −1 ) or saline (control) for 3 weeks via s.c. placed osmotic minipumps. During these 3 weeks, rats received i.p. injections of either STS, NaHS or vehicle (0.9% NaCl). KEY RESULTSCompared with controls, Ang II infusion caused an increase in systolic and diastolic BP with associated cardiac damage as evidenced by cardiac hypertrophy, an increase in atrial natriuretic peptide (ANP) mRNA, cardiac fibrosis and increased oxidative stress. Treatment with NaHS and STS prevented the development of hypertension and the increase in ANP mRNA levels. Furthermore, the degree of cardiac hypertrophy, the extent of histological fibrosis in combination with the expression of profibrotic genes and the levels of oxidative stress were all significantly decreased. CONCLUSIONS AND IMPLICATIONSAng II-induced hypertensive cardiac disease can be attenuated by treatment with STS and NaHS. Although BP regulation is the most plausible mechanism of cardiac protection, the antifibrotic and antioxidant properties of released sulfide may also contribute to their effects. Our data show that H2S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies. LINKED ARTICLESThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx

Exogenous Hydrogen Sulfide Attenuates Cardiac Fibrosis Through Reactive Oxygen Species Signal Pathways in Experimental Diabetes Mellitus Models

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