Hydrogen sulfide regulates lung tissue-oxidized glutathione and total antioxidant capacity in hypoxic pulmonary hypertensive rats

Abstract

To investigate the modulatory effect of sodium hydrosulfide on lung tissue-oxidized glutathione and total antioxidant capacity in the development of hypoxic pulmonary hypertension (HPH). 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. 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 micromol/L; 0.138+/-0.013 vs 0.289+/-0.036 nmol x mg(-1) x 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. 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.