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

Background and Purpose Hypertension is an important mediator of cardiac damage and remodelling. Hydrogen sulfide ( H 2 S ) 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 H 2 S donor substance, in angiotensin II ( A ng II )‐induced hypertensive cardiac disease in rats. Experimental Approach M ale S prague D awley rats were infused with A ng 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 Results Compared with controls, A ng 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 ) m RNA , cardiac fibrosis and increased oxidative stress. Treatment with NaHS and STS prevented the development of hypertension and the increase in ANP m RNA 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 Implications A ng 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 H 2 S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐6