title: Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats.
abstract: BACKGROUND
  The study was designed to explore the significance of endogenous H2S in the development of high-salt-induced hypertension in rats.
  
  
  METHODS
  High-salt-induced hypertension rat model was made by feeding Dahl rat high-salt diet containing 8% NaCl for 8 weeks with SD rats as control. SBP and aorta structure in rats were observed. Endogenous H2S content and expression of cystathionine β-lyase (CBS), cystathionine γ-lyase and mercaptopyruvate sulfurtransferase in renal tissues were detected. Mechanisms for the impact of high-salt on CBS/H2S in renal tissues were studied, targeting HIF-1α pathway. The effect of H2S on RAS in serum and renal tissue of rats were tested.
  
  
  RESULTS
  High-salt reduced endogenous H2S content and inhibited the expression of CBS in renal tissue in salt-sensitive Dahl rats. H2S donor, however, inhibited salt-sensitive hypertension, reversed aortic structural remodeling and inhibited activation of the RAS system in renal tissues in Dahl rats. Expression of HIF-1α was decreased but expression of PHD2 was increased in renal tissue of Dahl rats with high-salt diet, whereas they did not alter in renal tissue of SD rats with high-salt diet. Ex vivo experiment showed that inhibitor of HIF-1α degradation could rescue down-regulated CBS/H2S pathway in renal tissue of Dahl rats with high-salt. In contrast, inhibitor of HIF-1α activity decreased the CBS/H2S pathway in the renal tissue of SD rats treated with high-salt.
  
  
  CONCLUSIONS
  Down-regulated CBS/H2S pathway in renal tissues under high-salt insult might be an important pathogenesis of salt-sensitive hypertension.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Siyao
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Qiuyu
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Lab of Electric Microscopy, Peking University First Hospital, Beijing 100034, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Central Laboratory, Peking University First Hospital, Beijing 100034, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China; Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Animal Center, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Animal Center, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China; Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Electronic address: jinhongfang51@126.com.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008190:Lyases / Q000378:metabolism*; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D012965:Sodium Chloride; D008190:Lyases; C019965:cystathionine beta-lyase; D006862:Hydrogen Sulfide
keywords: Hydrogen sulfide; Hypertension; Kidney; Salt