Role of endogenous hydrogen sulfide in pulmonary hypertension induced by lipopolysaccharide

The purpose of the present study was to explore the role of endogenous hydrogen sulfide (H2S) in pulmonary arterial hypertension induced by endotoxin. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group (0.5 mL/kg body weight of normal saline, i.v.), lipopolysaccharide (LPS)-treated group (5 mg/kg body weight of LPS, i.v.), LPS + NaHS (5 mg/kg body weight of LPS, i.v., and 28 μmol/kg body weight of NaHS, i.p.) and LPS + PPG group (5 mg/kg body weight of LPS, i.v., and 30 μmol/kg body weight of PPG, i.p.). Rats were anesthetized with 20% urethane (1 g/kg body weight, i.p.). A polyethylene catheter was inserted into the pulmonary artery through the right external jugular vein to measure the mean pulmonary arterial pressure (mPAP) for 7 h, and then the pulmonary artery was isolated rapidly by the method described previously. Pulmonary arterial activity was detected. H2S concentration and cystathionine γ-lyase (CSE) activity in pulmonary artery tissues were determined by biochemical method. CSE mRNA expression was detected by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with control, LPS significantly increased mPAP [(1.82±0.29) kPa vs (1.43±0.26) kPa, P0.01], decreased H2S production [(26.33±7.84) vs (42.92±8.73) pmol/g wet tissue per minute, P0.01), and reduced endothelium-dependent relaxation response [(75.72±7.22)% vs (86.40±4.40)%, P0.01) induced by ACh (1×10-6 mol/L). These effects were partly reversed by co-administration of NaHS and enhanced by co- administration of PPG. Both CSE activity and CSE mRNA expression were consistent with H2S production. It is suggested that the inhibitory effect of LPS on endothelium-dependent relaxation results in pulmonary hypertension, which might be mediated through H2S.