Contribution of hydrogen sulfide and nitric oxide to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats

Mol Cell Biochem. 2013 Mar;375(1-2):199-206. doi: 10.1007/s11010-012-1542-1. Epub 2012 Dec 15.


It is well known that exercise training attenuates aortic remodeling and improves endothelial function in spontaneously hypertensive rats (SHR). However, the underlying molecular mechanism remains unclear. Hydrogen sulfide (H(2)S) and nitric oxide (NO), as two established physiologic messenger molecules, have important roles in the development of aortic remodeling and endothelial dysfunction in hypertensive animals and patients. In this work, it was found that exercise training had no significant effect on blood pressure, but effectively attenuated baroreflex dysfunction in SHR. Exercise training in SHR attenuated aortic remodeling and improved endothelium-mediated vascular relaxations of aortas in response to acetylcholine. Interestingly, exercise training in SHR restored plasma H(2)S levels and aortic H(2)S formation and enhanced levels of mRNA for cystathionine γ-lyase in aortas. Furthermore, exercise training in SHR resulted in augmentation of nitrite and nitrate (NOx) contents and reduction of asymmetric dimethylarginine contents of aortas, upregulation of dimethylarginine dimethylaminohydrolase 2, and phosphorylation of nitric oxide synthase 3, but had no significant effect on protein levels of NOS3. In addition, exercise training could effectively reduce malondialdehyde production and suppressed formation of O(2) (-), and OONO(-) in aortas of SHR through enhancing activities of superoxide dismutase and catalase, and suppressing NADPH oxidase activity. In conclusion, exercise training ameliorates aortic hypertrophy and endothelial dysfunction, possibly via restoring bioavailabilities of hydrogen sulfide and nitric oxide in SHR.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism*
  • Aorta, Thoracic / pathology
  • Aorta, Thoracic / physiopathology
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Blood Pressure
  • Endothelial Cells / metabolism
  • Endothelial Cells / physiology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Exercise Therapy
  • Heart Rate
  • Hydrogen Sulfide / blood*
  • Hypertension / blood*
  • Hypertension / physiopathology
  • In Vitro Techniques
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / physiology*
  • Oxidative Stress
  • Physical Conditioning, Animal
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY


  • dimethylarginine
  • Nitric Oxide
  • Malondialdehyde
  • Arginine
  • Hydrogen Sulfide