Objective: To investigate whether induction of apoptosis of pulmonary artery smooth muscle cells (PASMCs) was involved in the mechanism responsible for the protective role of hydrogen sulfide in the development of pulmonary hypertension induced by high pulmonary blood flow.
Methods: In the present study, we used a rat model of high pulmonary blood flow induced pulmonary hypertension established by an abdominal aorta-inferior vena cava shunt operation. DL-Propargylglycine (PPG), an inhibitor of endogenous hydrogen sulfide production, was administrated intraperitoneally at a dose of 37.5mg/kg per day for 4 week since the shunting operation. On the other side, sodium hydrosulfide (NaHS), a hydrogen sulfide donor, was administrated intraperitoneally at a dose of 56 μmol/kg per day for 11 weeks since the shuntiong operation.
Results: After 4 week shunting operation, the apoptosis of PASMCs , expression of Fas and caspase-3 were significantly decreased (P<0.01), but expression of Bcl-2 significantly increased (P<0.01). PPG administration further promoted the apoptosis of PASMCs, downregulated the expression of Fas and caspase-3 (P<0.01), and increased the expression of Bcl-2 (P<0.01); After 11 weeks shunting operation, the apoptosis of PASMCs, expression of Fas and Caspase-3 were significantly decreased (P<0.01), but expression of Bcl-2 significantly increased (P<0.01). NaHS administration significantly increased the apoptosis of PASMCs, upregulated the expression of Fas and caspase-3, and inhibited the expression of Bcl-2.
Conclusion: Hydrogen sulfide might exert a protective role in the development of pulmonary hypertension induced by high pulmonary blood flow by inducing the apoptosis of PASMCs.