Acta Pharmacologica Sinica 2008 June; 29 (6): 670-676; doi: 10.1111/j.1745-7254.2008.00796.x

Aim: To investigate the modulatory effect of sudium hydrosulfide on lung tissue-oxidized glutathione and total antioxidant capacity in the development of hypoxic pulmonary hypertension (HPH).

Methods: After 21 d of hypoxia, the mean pulmonary artery pressure was measured by cardiac catheterization. The plasma H₂S level and production of H₂S in the lung tissues were determined by using a spectrophotometer. The lung homogenates were assayed for total antioxidant capacity (T-AOC), superoxide dismutase (SOD), oxidized glutathione (GSSG), reduced glutathione and malonaldehyde by colorimetry. The mRNA level of SOD was analyzed by real-time PCR, and the SOD expression was detected by Western blotting.

Results: In the hypoxia group, the plasma H₂S concentration and H₂S production in the lung was significantly decreased compared with the control group (187.2±13.1 vs 299.6±12.4 µmol/L; 0.138±0.013 vs 0.289±0.036 nmol·mg^-1·min^-1, P<0.01). The administration of sodium hydrosulfide could reduce the mean pulmonary artery pressure by 31.2% compared with the hypoxia group (P<0.01). Treatment with sodium hydrosulfide decreased GSSG, and the T-AOC level of the lung tissues was enhanced compared with the hypoxia group (P<0.05). There were no significant changes in the lung tissue SOD mRNA level, protein level, and its activity among the 3 groups.

Conclusion: Oxidative stress occurred in the development of HPH and was accompanied by a decrease in the endogenous production of H₂S in the lung tissues. H₂S acted as an antioxidant during the oxidative stress of HPH partly as a result of the attenuated GSSG content.

Keywords: hydrogen sulfide; oxidative stress; hypoxia; pulmonary hypertension; superoxide dismutase