title: The roles of nitric oxide and hydrogen sulfide in the anti-atherosclerotic effect of atorvastatin.
abstract: OBJECTIVE
  To investigate antiatherosclerosis effect of atorvastatin (ATV) in a rat atherosclerosis model, and to explore roles of nitric oxide and hydrogen sulfide (H2S) in this event.
  
  
  METHODS
  After being fed a high-fat diet, the rats were treated with ATV, ATV combined with cystathionine-γ-lyase (CSE) inhibitor DL-propargylglycine, and ATV combined with endothelial nitric oxide synthase (eNOS) inhibitor N'-nitro-L-arginine-methyl ester hydrochloride from 9 to 12 weeks, respectively. At the end of the experiment, the animals were sacrificed. Pathologic changes of aortic arch were observed to assay the degree of atherosclerotic lesions. Serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol were determined. Further, nitric oxide, total nitric oxide synthase and eNOS, and H2S and CSE were also measured.
  
  
  RESULTS
  Compared with the normal control group, serum TC, triglyceride, and LDL-C levels in the model group were significantly elevated (P < 0.05). Pathological result suggested typical atherosclerotic lesions after the high-fat diet. The serum nitric oxide, eNOS, H2S, and CSE significantly decreased (P < 0.05). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that mRNA levels of eNOS and CSE in the aortic arch of the model rats were significantly downregulated (P < 0.05). Actually, ATV significantly ameliorated atherosclerotic lesions. ATV also significantly downregulated increased serum TC and LDL-C, and upregulated decreased serum nitric oxide and eNOS. However, it had no significant effects on serum H2S and CSE (P > 0.05). ATV combined with DL-propargylglycine significantly reduced serum H2S and CSE, and increased serum nitric oxide and eNOS as compared to single ATV treatment (P < 0.05). ATV combined with N'-nitro-L-arginine-methyl ester hydrochloride significantly increased serum TC, LDL-C, H2S, and CSE, and decreased nitric oxide and eNOS as compared to the single ATV (P < 0.05).
  
  
  CONCLUSIONS
  ATV significantly ameliorates atherosclerotic lesions and enhances the activity of serum nitric oxide system, but not H2S system. The blockage of nitric oxide pathway, but not H2S pathway, significantly weakens antiatherosclerosis of ATV.
authors.affiliation: aDepartment of Cardiology, The Affiliated Hospital of Luzhou Medical College, Luzhou bDepartment of Cardiology, Santai People's Hospital, Santai, Sichuan Province, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Dongming
authors.initials: D
authors.lastname: Ma
authors.forename: Shuzhan
authors.initials: S
authors.lastname: Zheng
authors.forename: Kelan
authors.initials: K
authors.lastname: Zha
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Yihua
authors.initials: Y
authors.lastname: Cai
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Jiafu
authors.initials: J
authors.lastname: Li
authors.forename: Zhongcai
authors.initials: Z
authors.lastname: Fan
mesh_terms: D000480:Alkynes; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000069059:Atorvastatin; D059305:Diet, High-Fat; D005998:Glycine / Q000031:analogs & derivatives; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley
chemical_list: D000480:Alkynes; D006538:Heptanoic Acids; D011758:Pyrroles; D009569:Nitric Oxide; C009055:propargylglycine; D000069059:Atorvastatin; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester; D006862:Hydrogen Sulfide