[Impact of hydrogen sulfide donor on experimental pulmonary hypertension induced by high pulmonary flow and endogenous carbon monoxide/heme oxygenase pathway].
OBJECTIVE
To explore the possible impact of hydrogen sulfide donor-NaHS (sodium hydrosulfide) on experimental pulmonary artery structural remodeling induced by high pulmonary flow and endogenous carbon monoxide/heme oxygenase pathway.


METHODS
Thirty-two male SD rats were randomly divided into shunt group (n=8), shunt+NaHS group (n=8), sham group (n=8) and sham+NaHS group (n=8). Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the sham group and sham+NaHS group, rats experienced the same experimental processes except the shunting procedure. After 11 weeks of operation, systolic pulmonary artery pressure (SPAP) was detected using a right cardiac catheterization procedure. The percentage of muscularized artery (MA), partly muscularized artery (PMA) and non-muscularized artery (NMA) was calculated. Relative medial thickness (RMT) and relative medial area (RMA) of MA were observed under optical-microscope, respectively. The ultra-structure of pulmonary arteries was observed under electro-microscope. Lung tissue carbon monoxide (CO) was measured. Western-blot was used to analyze lung tissue heme oxygenase (HO-1) protein expression.


RESULTS
After 11 weeks of shunt, compared with sham group, SPAP in shunt group increased by 48.6%.The percentages of MA and PMA increased by 74.2% and 90.9%, but the percentage of NMA decreased 32.2%, respectively, in rats of shunt group as compared with that of sham group. In contrast to those in sham group, RMT and RMA in median MA and small MA of rats in shunt group increased by 83.6%, 86.9%, and 74.4%, 39.9%, respectively. Ultra-structural changes in rats of shunt group showed that endothelial cells were swollen and denatured, inner elastic membrane became irregular, and smooth muscle cells became synthetic phenotype. The sham and shunt groups did not differ significantly in CO and HO-1 protein expression of lung tissues. In contrast to that of shunt group, SPAP in rats of shunt+NaHS group decreased by 19.8%. The percentages of MA and PMA decreased by 14.4% and 12.2%, but the percentage of NMA increased 13.9%, respectively, in rats of shunt+NaHS group as compared with that of shunt group. In contrast to those of shunt group, RMT and RMA in median MA and small MA in rats of shunt+NaHS group decreased by 16.2%, 14.3%, and 26.9%, 14.3%, respectively. For rats in shunt+NaHS group ultra-structural changes showed that flat endothelial cells, inner elastic membrane became regular, and smooth muscle cells were contractile phenotype. The content of CO increased by 25.5% and the HO-1 protein expression increased by 114.3% in shunt+NaHS group as compared with those of shunt group.


CONCLUSIONS
NaHS might prevent pulmonary hypertension and pulmonary artery structural remodeling induced by high pulmonary flow, and its mechanism might be associated with the changes in endogenous CO/HO pathway.
Li
Xiao-hui
XH
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Du
Jun-bao
JB
Ding
Ya-guang
YG
Jin
Hong-fang
HF
Bu
Ding-fang
DF
Tang
Xiu-ying
XY
Tang
Chao-shu
CS
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000378:metabolism*
D013440:Sulfides; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C025451:sodium bisulfide