title: Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II-induced hypertensive heart disease in rats.
abstract: OBJECTIVE
  Hypertension 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 H2 S donor substance, in angiotensin II (Ang II)-induced hypertensive cardiac disease in rats.
  
  
  METHODS
  Male 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).
  
  
  RESULTS
  Compared 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
  Ang 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 H2 S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies.
authors: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: P M
authors: PM
authors: Snijder
authors: A R
authors: AR
authors: Frenay
authors: R A
authors: RA
authors: de Boer
authors: A
authors: A
authors: Pasch
authors: J L
authors: JL
authors: Hillebrands
authors: H G D
authors: HG
authors: Leuvenink
authors: H
authors: H
authors: van Goor
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology*; D013885:Thiosulfates / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D013440:Sulfides; D013885:Thiosulfates; D000804:Angiotensin II; C025451:sodium bisulfide; C017717:sodium thiosulfate; D006862:Hydrogen Sulfide