title: Involvement of Hydrogen Sulfide in Endothelium-Derived Relaxing Factor-Mediated Responses in Rat Cerebral Arteries.
abstract: OBJECTIVE
  H2S is a novel vasoactivator. To verify the hypothesis that H2S may act as an endothelium-derived hyperpolarizing factor (EDHF) in the rat cerebrovasculature, the role of H2S in endothelium-derived relaxing factor (EDRF)-mediated responses was investigated.
  
  
  METHODS
  Cystathionine-γ-lyase (CSE) was knocked down with an siRNA technique. Artery diameter, hyperpolarization and Ca2+-activated K+ (KCa) current were measured.
  
  
  RESULTS
  CSE knockdown was indicated by a decrease in protein and mRNA expression in the rat middle cerebral artery (MCA) and cerebral basilar artery (CBA). Acetylcholine (ACh) induced significant hyperpolarization and vasodilation in endothelium-intact MCA and CBA. Removal of the endothelium abolished these responses. The nitric oxide (NO) synthase inhibitor L-NAME, but not the PGI2 production inhibitor indomethacin, significantly inhibited ACh-induced hyperpolarization and vasodilation in the CBA. In the presence of L-NAME and indomethacin, ACh-induced hyperpolarization and vasodilation in the MCA and CBA were attenuated. The non-NO/PGI2-mediated responses were abolished by the KCa channel blockers charybdotoxin and apamin. In the cerebral arteries from the CSE knockdown rat, non-NO/PGI2-mediated responses were significantly attenuated, and the remaining responses were abolished by charybdotoxin and apamin or the CSE inhibitor propargylglycine. CSE knockdown did not affect L-NAME-sensitive responses in the CBA. Sodium hydrosulfide (NaHS) augmented the KCa current in CBA vascular smooth muscle cells.
  
  
  CONCLUSIONS
  EDHF-mediated responses in rat cerebral arteries were due to H2S activating the KCa channel.
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Youyang
authors.initials: Y
authors.lastname: Hu
authors.forename: Yifei
authors.initials: Y
authors.lastname: Fan
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Fanglin
authors.initials: F
authors.lastname: Chen
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D001685:Biological Factors / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D034741:RNA, Small Interfering; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide