Aim: The present study aimed to explore the protective effect of endogenous sulfur dioxide (SO 2 ) in the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Methods: Forty Wistar rats were randomly divided into the MCT group receiving MCT treatment, the MCT+L-aspartate-β-hydroxamate (HDX) group receiving MCT plus HDX treatment, the MCT+SO 2 group receiving MCT plus SO 2 donor treatment, and the control group. Mean pulmonary artery pressure (mPAP) and structural changes in pulmonary arteries were evaluated. SO 2 content, aspartate aminotransferase activity, and gene expression were measured. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), reduced glutathione (GSH), oxidized glutathione, and malondialdehyde (MDA) levels were assayed. Results: In the MCT-treated rats, mPAP and right ventricle/(left ventricle+septum) increased significantly (P<0.01), pulmonary vascular structural remodeling developed, and SOD, GSHPx, CAT, GSH, and MDA levels of lung homogenates significantly increased (P<0.01) in association with the elevated SO 2 content, aspartate aminotransferase activity, and gene expression, compared with the control rats. In the MCT+HDX-treated rats, lung tissues and plasma SO 2 content and aspartate aminotransferase activities decreased significantly, whereas the mPAP and pulmonary vascular structural remodeling were markedly aggravated with the decreased SOD, CAT, and GSH levels of lung tissue homogenates compared with the MCTtreated rats (P<0.01). In contrast, with the use of a SO 2 donor, the pulmonary vascular structural remodeling was obviously lessened with elevated lung tissue SOD, GSH-Px, and MDA content, and plasma SOD, GSH-Px, and CAT levels. Conclusion: Endogenous SO 2 might play a protective role in the pathogenesis of MCT-induced PH and promote endogenous antioxidative capacities.

Recently, sulfur dioxide (SO 2 ) was discovered to be produced in the cardiovascular system and to influence important biological processes. Here, we investigated changes in endogenous SO 2 /glutamic oxaloacetic transaminase (GOT) pathway in the development of isoproterenol (ISO)-induced myocardial injury in rats and the regulatory effect of SO 2 on cardiac function, myocardial micro-and ultrastructure, and oxidative stress. Wistar male rats were divided into control, ISO-treated, ISO þ SO 2 , and SO 2 groups. At the termination of the experiment, parameters of cardiac function and hemodynamics were measured and the micro-and ultrastructure of myocardium and stereological ultrastructure of mitochondria were analyzed. Myocardial SO 2 content was detected by high-performance liquid chromatography. GOT (key enzyme for endogenous SO 2 production) activity and gene (GOT1 and GOT2) expressions were measured, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), hydrogen peroxide, and superoxide radical levels were assayed. SOD (SOD1 and SOD2) and GSH-Px (GSH-Px1) gene expressions were also detected. The results showed that SO 2 donor at a dose of 85 mg/(kg day) did not impact the cardiac function and structure of rats, but exerted a subtle influence on myocardial redox status. ISO-treated rats exhibited decreased cardiac function, damaged myocardial structures, and downregulated endogenous SO 2 /GOT pathway. Meanwhile, myocardial oxidative stress increased, whereas antioxidative capacity downregulated. Administration of SO 2 markedly improved cardiac function and ISO-induced myocardial damage by ameliorating the pathological structure of the myocardium and the mitochondria. At the same time, myocardial products of oxidative stress decreased, whereas antioxidative capacity increased. These results suggest that downregulation of the endogenous SO 2 /GOT pathway is likely involved in the pathogenesis of ISO-induced myocardial injury. SO 2 protects against ISO-induced myocardial injury associated with increased myocardial antioxidant capacity in rats.

Aim: To investigate the interaction between hydrogen sulfide (H 2 S)/cystathionine γ-lyase (CSE) and carbon monoxide (CO)/heme oxygenase (HO) pathways in aortic smooth muscle cells (ASMC). Methods: The ASMCs were divided into the following groups: (1) the control group; (2) the zinc protoporphyrin (ZnPP) 20 µmol/L group; (3) the propargylglycine (PPG) 2 mmol/L, 4 mmol/L and 10 mmol/L groups; and (4) the sodium hydrosulfide (NaHS) 1×10-5 mol/L, 1×10 -4 mol/L and 1×10 -3 mol/L groups. Each of the groups was further divided into 6 h, 12 h, 18 h and 24 h subgroups. The CO level, represented by carboxyhemoglobin (HbCO) content was measured using a spectrophotometric method and H 2 S content was detected by a sensitive electrode method. CSE and HO-1 expressions were detected by Western blotting. Results: The H 2 S content in the medium and CSE expression by ASMC were markedly increased by ZnPP compared with the control group. HbCO content in the medium and HO-1 expression by the ASMC started strengthening following 24 h treatment with PPG at 2 mmol/L, but were further strengthened following 18 h and 24 h treatment with PPG at 4 mmol/L compared with the controls (P<0.01). PPG at 10 mmol/L increased the HbCO level in the medium following 18 h treatment and increased HO-1 expression by the ASMC following 12 h treatment. Moreover, NaHS at 1×10 -5 mol/L and 1×10 -4 mol/L decreased the HbCO level in the medium and HO-1 expression by the ASMC after 6 h and 12 h treatment, while NaHS at 1×10 -3 mol/L decreased them at all time points of the treatments. Conclusion: The results suggested that endogenous CO/HO and H 2 S/CSE pathways inhibited each other in ASMC under physiological conditions.

Endogenous SO2 might be involved in the pathogenesis of myocardial I/R injury, and its mechanism might be associated with an increase in lipid peroxide level and a decrease in GSH generation.

It has been demonstrated that excessively activated endoplasmic reticulum stress (ERS) is related to myocardial injury. The study was designed to explore the possible role of sulfur dioxide (SO(2)) in protecting excessively activated ERS in rats with isoproterenol (ISO)-induced myocardial injury. Wistar rats were randomly divided into control, ISO, and ISO + SO(2) groups. Cardiac catheterization-derived hemodynamic parameters and myocardial enzymes in plasma were measured. Microstructure changes in myocardial tissues were examined. Cardiomyocyte apoptosis was detected by TUNEL method. Myocardial SO(2) content and aspartate amino transferase (AAT) activity were detected. Meanwhile, protein and mRNA expressions of myocardial AAT1, AAT2, and ERS markers (GRP78, caspase-12, and CHOP) were evaluated. The results showed that cardiac function was decreased, myocardial microstructure was damaged, and myocardial enzyme levels and cardiomyocyte apoptosis were increased with a downregulated endogenous AAT/SO(2) pathway, and that ERS markers were upregulated at transcriptional and translational levels in ISO-treated rats. However, the administration of an SO(2) donor, resulting in an increased SO(2) content in myocardial tissues, improved cardiac function and myocardial structure, and ameliorated myocardial enzyme levels and cardiomyocyte apoptosis associated with a downregulation of excessively activated ERS. In conclusion, the endogenous AAT/SO(2) pathway was probably responsible for the inhibition of excessively activated ERS, which might be involved in the mechanism of ISO-induced myocardial injury.