title: MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery.
abstract: Hydrogen sulfide (H2S) has emerged as an important gasotransmitter in the vasculature. In this study, we tested the hypothesis that H2S contributes to coronary vasoregulation and evaluated the physiological relevance of two sources of H2S, namely, cystathionine-γ-lyase (CSE) and 3-mercaptypyruvate sulfertransferase (MPST). MPST was detected in human coronary artery endothelial cells as well as rat and mouse coronary artery; CSE was not detected in the coronary vasculature. Rat coronary artery homogenates produced H2S through the MPST pathway but not the CSE pathway in vitro. In vivo coronary vasorelaxation response was similar in CSE knockout mice, wild-type mice (WT), and WT mice treated with the CSE inhibitor propargylglycine, suggesting that CSE-produced H2S does not have a significant role in coronary vasoregulation in vivo. Ex vivo, the MPST substrate 3-mercaptopyruvate (3-MP) and H2S donor sodium hydrosulfide (NaHS) elicited similar coronary vasoreactivity responses. Pyruvate did not have any effects on vasoreactivity. The vasoactive effect of H2S appeared to be nitric oxide (NO) dependent: H2S induced coronary vasoconstriction in the presence of NO and vasorelaxation in its absence. Maximal endothelial-dependent relaxation was intact after 3-MP and NaHS induced an increase in preconstriction tone, suggesting that endothelial NO synthase activity was not significantly inhibited. In vitro, H2S reacted with NO, which may, in part explain the vasoconstrictive effects of 3-MP and NaHS. Taken together, these data show that MPST rather than CSE generates H2S in coronary artery, mediating its effects through direct modulation of NO. This has important implications for H2S-based therapy in healthy and diseased coronary arteries.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Kuo
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Anethesiology and Pain Medicine, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Dae Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Sandeep
authors.initials: S
authors.lastname: Jandu
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Bergman
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Siqi
authors.initials: S
authors.lastname: Tan
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Huilei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Deepesh R
authors.initials: DR
authors.lastname: Pandey
authors.affiliation: Department of Medicine (Cardiology), Johns Hopkins University, Baltimore, Maryland; and.
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Abraham
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Artin A
authors.initials: AA
authors.lastname: Shoukas
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; LSantha1@jhmi.edu.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Santhanam
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology*; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013466:Sulfurtransferases / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: 3-mercaptopyruvate sulfurtransferase; coronary tone; coronary vasoregulation; cystathionine-γ-lyase; hydrogen sulfide