Hydrogen Sulfide Improves Myocardial Remodeling via Downregulated Angiotensin Ⅱ/AT1R Pathway in Renovascular Hypertensive Rats

Am J Hypertens. 2017 Jan;30(1):67-74. doi: 10.1093/ajh/hpw104. Epub 2016 Sep 6.

Abstract

Background: Hydrogen sulfide (H2S) is an important endogenous gaseous transmitter in many physiological functions. Plasma H2S decreased, and angiotensin II (Ang II) type 1 receptor (AT1R) increased in the myocardial tissues in 2-kidney 1-clip (2K1C) rats than in normotensive rats. Accumulating evidences suggest that H2S inhibited Ang II/AT1R pathway to regulate cardiovascular function. Therefore, we hypothesized that H2S may exert beneficial effects on myocardial remodeling in 2K1C rat models of renovascular hypertension.

Methods and results: Sodium hydrosulfide (NaHS, 56 µmol/kg/day) was administered intraperitoneally to the rats from the 7th day after 2K1C operation. Systolic blood pressure was significantly increased from the first week after the operation and was lowered after NaHS treatment for 4 weeks. H2S could also inhibit the ratio of left ventricle and septum weight to body weight, improve cross-sectional area, and ameliorate ventricular dysfunction. Additionally, the protein expression of AT1R and Ang II serum content were downregulated, whereas superoxide dismutase (SOD) protein was upregulated in 2K1C rats by NaHS treatment for 4 weeks. Furthermore, the reactive oxygen species level and AT1R protein were increased, whereas SOD protein was decreased in cardiomyocytes treated with Ang II compared with the control group. NaHS could reverse these changes. Losartan and N-acetylcysteine could also reverse Ang II-induced changes.

Conclusions: The protective effect of H2S is attributable to the suppression of oxidative stress. This process involves the inhibition of the Ang II/AT1R pathway and upregulation of antioxidant enzymes in 2K1C rats.

Keywords: angiotensin II type 1 receptor; blood pressure; hydrogen sulfide; hypertension; myocardial remodeling; reactive oxygen species..

MeSH terms

  • Angiotensin II / blood
  • Animals
  • Blood Pressure / drug effects
  • Cardiomegaly / etiology
  • Cardiomegaly / prevention & control*
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Gasotransmitters / pharmacology
  • Gasotransmitters / therapeutic use*
  • Hydrogen Sulfide / blood
  • Hydrogen Sulfide / pharmacology
  • Hydrogen Sulfide / therapeutic use*
  • Hypertension, Renovascular / complications*
  • Hypertension, Renovascular / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / metabolism
  • Superoxide Dismutase-1 / metabolism
  • Ventricular Remodeling / drug effects*

Substances

  • Gasotransmitters
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • Sod1 protein, rat
  • Superoxide Dismutase-1
  • Hydrogen Sulfide