title: Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide.
abstract: BACKGROUND
  The potential biological significance of hydrogen sulfide (H(2)S) has attracted growing interest in recent years. The aim of this study was to characterize a novel, water-soluble, slow-releasing H(2)S compound [morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate (GYY4137)] and evaluate its use as a tool to investigate the cardiovascular biology of this gas.
  
  
  RESULTS
  The acute vasorelaxant effect of drugs was assessed in rat aortic rings and perfused rat kidney in vitro and in the anesthetized rat in vivo. The chronic effect of GYY4137 on blood pressure in normotensive and spontaneously hypertensive rats was determined by tail-cuff plethysmography. GYY4137 released H(2)S slowly both in aqueous solution in vitro and after intravenous or intraperitoneal administration in anesthetized rats in vivo. GYY4137 caused a slow relaxation of rat aortic rings and dilated the perfused rat renal vasculature by opening vascular smooth muscle K(ATP) channels. GYY4137 did not affect rat heart rate or force of contraction in vitro. GYY4137 exhibited antihypertensive activity as evidenced by ability to reduce N(G)-nitro-L-arginine methyl ester-evoked hypertension in the anesthetized rat and after chronic (14-day) administration in spontaneously hypertensive rats.
  
  
  CONCLUSIONS
  These results identify GYY4137 as a slow-releasing H(2)S compound with vasodilator and antihypertensive activity. GYY4137 is likely to prove useful in the study of the many and varied biological effects of H(2)S. GYY4137 may also prove of therapeutic value in cardiovascular disease.
authors.affiliation: Department of Pharmacology, National University of Singapore, Singapore
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Matthew
authors.initials: M
authors.lastname: Whiteman
authors.forename: Yan Yi
authors.initials: YY
authors.lastname: Guan
authors.forename: Kay Li
authors.initials: KL
authors.lastname: Neo
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Cheng
authors.forename: Shiau Wei
authors.initials: SW
authors.lastname: Lee
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Rajamanian
authors.initials: R
authors.lastname: Baskar
authors.forename: Choon-Hong
authors.initials: CH
authors.lastname: Tan
authors.forename: Philip K
authors.initials: PK
authors.lastname: Moore
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology; D014867:Water
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D014665:Vasodilator Agents; D014867:Water; D006862:Hydrogen Sulfide