The regulatory effect of endogenous hydrogen sulfide on pulmonary vascular structure and gasotransmitters in rats with high pulmonary blood flow.
The study aimed to explore the regulatory effect of endogenous hydrogen sulfide (H(2)S), a novel gasotransmitter, on pulmonary vascular structure and gasotransmitters in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham+PPG (propargylglycine, an inhibitor of cystathionine-gamma-lyase) group and shunt+PPG group. Rats in the shunt and shunt+PPG groups underwent abdominal aorta-inferior vena cava shunting. Rats in the shunt+PPG and sham+PPG groups were intraperitoneally injected with PPG. After 4 weeks of shunting, mean pulmonary artery pressure (MPAP) and pulmonary vascular structural remodeling (PVSR) were evaluated. H(2)S, nitric oxide (NO) and carbon monoxide (CO) contents were measured in lung tissues. Meanwhile, nitric oxide synthase (eNOS), heme oxygenase (HO-1) and proliferative cell nuclear antigen (PCNA) protein expressions and ERK activation were evaluated. After 4 weeks of shunting, rats showed PVSR with increased lung tissue H(2)S and NO content but decreased CO content. After the PPG treatment, MPAP further increased and PVSR was aggravated. Meanwhile, PCNA expression and ERK activation were augmented with decreased lung tissue CO and HO-1 protein production but increased lung tissue NO production and eNOS expression. H(2)S exerted a protective effect on PVSR, and the inhibition of the NO/NOS pathway and the augmentation of the CO/HO pathway might be involved in the mechanisms by which H(2)S regulates PVSR in rats with high pulmonary flow.
Li
Xiaohui
X
Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, Beijing, 100034, People's Republic of China.
Du
Junbao
J
Jin
Hongfang
H
Tang
Xiuying
X
Bu
Dingfang
D
Tang
Chaoshu
C
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D001166:Arteriovenous Shunt, Surgical; D002248:Carbon Monoxide / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000032:analysis / Q000378:metabolism*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014682:Vena Cava, Inferior / Q000601:surgery
D000480:Alkynes; D018809:Proliferating Cell Nuclear Antigen; D009569:Nitric Oxide; C009055:propargylglycine; D002248:Carbon Monoxide; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide