Regulatory effects of sulfur dioxide on the development of atherosclerotic lesions and vascular hydrogen sulfide in atherosclerotic rats

Objective: This study was designed to examine the effect of sulfur dioxide (SO2) on atherosclerotic progression and endogenous vascular hydrogen sulfide (H2S) in rats with atherosclerosis (AS). Methods: Twenty-eight male rats were randomly divided into control, AS and AS + SO2 groups. Rats were given a single dose of vitamin D-3 and fed a high-cholesterol diet for 8 weeks to induce AS. Plasma lipids, aortic ultrastructure, and atherosclerotic lesions were detected at the termination of experiment. Plasma and aortic SO2 were measured using high-performance liquid chromatography, and aspartate aminotransferase (AAT) 1 and AAT2 mRNAs were detected by real-time PCR. Plasma and aortic H2S levels were determined with a sulfide-sensitive electrode. Cystathionine-gamma-lyase (CSE) mRNA and protein expression was detected. Plasma glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) and nitric oxide (NO) contents, inducible NO synthase (iNOS) and eNOS activities, and aortic SOD1 and SOD2 expressions were detected. Results: Marked atherosclerotic lesions with elevated levels of TC and LDL-C were observed in AS rats. While, there were decreased plasma SO2 levels and aortic SO2 production, with a reduced aortic AAT activity in atherosclerotic rats. Plasma GSH-Px and SOD activities were decreased but MDA level increased. Plasma NO content and iNOS activity were also increased. SO2 donor, however, significantly decreased the atherosclerotic lesions with an increased aortic H2S/CSE pathway. It elevated plasma GSH-Px and SOD activities, reduced plasma MDA level, and increased NO/NOS pathway. Conclusions: SO2 has a marked anti-atherogenic effect with an increase in endogenous H2S production in rats with AS. (C) 2011 Elsevier Ireland Ltd. All rights reserved.