title: Sulfur dioxide upregulates the inhibited endogenous hydrogen sulfide pathway in rats with pulmonary hypertension induced by high pulmonary blood flow.
abstract: Pulmonary hypertension (PH) is an important pathophysiological process in the development of many diseases. However, the mechanism responsible for the development of PH remains unknown. The objective of the study was to explore the possible impact of sulfur dioxide (SO2) on the endogenous hydrogen sulfide (H2S) pathway in rats with PH induced by high pulmonary blood flow. Compared with sham group, the systolic pulmonary artery pressure (SPAP) in the shunt group was significantly increased, along with the increased percentage of muscularized arteries and partially muscularized arteries of small pulmonary arteries. Compared with the shunt group, SPAP in the shunt+SO2 group was significantly decreased, and the percentage of muscularized pulmonary arteries was also decreased. Additionally, rats that developed PH had significantly lower levels of SO2 concentration, aspartate aminotransferase (AAT) activity, protein and mRNA expressions of AAT2 in pulmonary tissues. Administration of an SO2 donor could alleviate the elevated pulmonary arterial pressure and decrease the muscularization of pulmonary arteries. At the same time, it increased the H2S production, protein expression of cystathionine-γ-lyase (CSE), mRNA expression of CSE, mercaptopyruvate transsulphurase (MPST) and cystathionine-β-synthase (CBS) in the pulmonary tissue of the rats. The results suggested that endogenous SO2/AAT2 pathway and the endogenous H2S production were downregulated in rats with PH induced by high pulmonary blood flow. However, SO2 could reduce pulmonary arterial pressure and improve the pulmonary vascular pathological changes in association with upregulating endogenous H2S pathway.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Liman
authors.initials: L
authors.lastname: Luo
authors.forename: Die
authors.initials: D
authors.lastname: Liu
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.forename: Angie Dong
authors.initials: AD
authors.lastname: Liu
authors.forename: Lukas
authors.initials: L
authors.lastname: Holmberg
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001794:Blood Pressure; D015153:Blotting, Western; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013458:Sulfur Dioxide / Q000494:pharmacology*; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D013458:Sulfur Dioxide; D001219:Aspartate Aminotransferases; D013466:Sulfurtransferases; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide