Objective: To study the changes of endogenous H2S and the effect of exogenously applied H2S on hypoxic pulmonary hypertension (HPH).
Methods: Male Wistar rats were randomly divided into control group (n = 6), hypoxia group (n = 7) and hypoxia + NaHS group (n = 6). The rats that received hypoxia were put into a normobaric hypoxic chamber to respire hypoxic gas containing 10% (volume fraction) O2 for 6 hours everyday. NaHS solution was injected to rats of hypoxia + NaHS group at a dosage of 0.78 mg.kg-1 before hypoxic challenge. After 21 days of hypoxia, the mean pulmonary artery pressure (mPAP) was measured. The weight ratio of right ventricle vs left ventricle and septum [RV/(LV + SP)] was measured. The microstructure and ultrastructure changes in pulmonary small arteries were examined using elastin staining and transparent electron microscope respectively. And the activity of H2S generating enzymes in homogenates of the lung tissue and pulmonary artery was measured. The cystathionine gamma--lyase (CSE) mRNA in lung tissue was also measured using quantitative RT-PCR.
Results: Compared with rats in the control group, the mPAP increased 45.6% (P < 0.01) and the RV/(LV + SP) ratio increased 41% (P < 0.01) in rats of hypoxia group respectively. The relative medium thickness (RMT) and relative medium areas (RMA) increased 41% and 49% respectively (P all < 0.01) under optical microscope. The ultrastructure of the pulmonary small arteries also changed significantly. The H2S generating enzyme activity in lung tissue and in pulmonary artery decreased 52% and 54% respectively (P < 0.01). There were obviously negative correlations between the mPAP and H2S generating enzymes ativity. Relative CSE mRNA amount in lung tissue also decreased 53% (P < 0.01) in rats of hypoxia group compared with that of control group. The mPAP, and the RV/(LV + SP) ratio of rats in hypoxia + NaHS group decreased 31.2%, and 24% respectively compard with that of hypoxia group (P < 0.01). The RMT and RMA in rats of hypoxia + NaHS group also decreased 36% and 31% respectively (P < 0.01). In hypoxia + NaHS group, the H2S generating enzymes activity and relative CSE mRNA amount in the lung tissue increased 67.7% and 110% respectively compared with those in hypoxia group (P all < 0.01).
Conclusion: Endogenous H2S was involved in the pathogenesis of rat's HPH. Exogenously applied H2s could exert protective effect during HPH.