Sodium hydrosulfide alleviated pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats.
OBJECTIVE
To explore the possible role of endogenous hydrogen sulfide (H(2)S), a novel gasotransmitter, in the pathogenesis of pulmonary vascular structural remodeling (PVSR) induced by high pulmonary blood flow.


METHODS
Thirty-two Sprague-Dawley male rats were randomly divided into sham, shunt, sham+NaHS (a H(2)S donor) and shunt+NaHS groups. Rats in shunt and shunt+NaHS groups underwent an abdominal aorta-inferior vena cava shunt, and rats in shunt+NaHS and sham+NaHS groups were intraperitoneally injected with NaHS. PVSR was investigated using optical microscope and transmission electron microscope. Lung tissue H(2)S was evaluated by sulfide-sensitive electrodes. Nitric oxide synthase (NOS), heme oxygenase (HO-1), proliferative cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) activation were analyzed by Western blotting.


RESULTS
After 11 weeks of shunting, PVSR developed with a decrease in lung tissue H(2)S production and an increase in nitric oxide (NO). However, lung tissue carbon monoxide (CO) did not change. After the treatment with NaHS for 11 weeks, H(2)S donor ameliorated PVSR and downregulated PCNA expression and ERK activation with an increase in lung tissue CO production and HO-1 protein expression but a decrease in NO production, NOS activity and eNOS protein expression in shunted rats.


CONCLUSIONS
H(2)S exerted a regulatory effect on PVSR induced by high pulmonary blood flow. Meanwhile, H(2)S down-regulated the ERK/MAPK signal pathway, inhibited the NO/NOS pathway and enhanced the CO/HO pathway in rats with high pulmonary blood flow.
Li
Xiao-Hui
XH
Department of Pediatrics, Peking University First Hospital, Key Laboratory of Molecular Cardiovascular Diseases, Ministry of Education, Peking University First Hospital, Beijing 100034, China.
Du
Jun-Bao
JB
Bu
Ding-Fang
DF
Tang
Xiu-Ying
XY
Tang
Chao-Shu
CS
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D002248:Carbon Monoxide / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000473:pathology*; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology; D011652:Pulmonary Circulation / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013440:Sulfides / Q000494:pharmacology*
D018809:Proliferating Cell Nuclear Antigen; D013440:Sulfides; D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006419:Heme Oxygenase (Decyclizing); D048049:Extracellular Signal-Regulated MAP Kinases; C025451:sodium bisulfide; D006862:Hydrogen Sulfide