The roles of nitric oxide and hydrogen sulfide in the anti-atherosclerotic effect of atorvastatin

Abstract

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. 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. 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). 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.