title: Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic inhibition.
abstract: OBJECTIVE
  Hydrogen sulfide (H(2)S) at low concentrations serves as a physiological endogenous vasodilator molecule, while at higher concentrations it can trigger cytotoxic effects. The aim of our study was to elucidate the potential mechanisms responsible for the effects of H(2)S on vascular tone.
  
  
  METHODS
  We measured the vascular tone in vitro in precontracted rat thoracic aortic rings and we have tested the effect of different oxygen levels and a variety of inhibitors affecting known vasodilatory pathways. We have also compared the vascular effect of high concentrations of H(2)S to those of pharmacological inhibitors of oxidative phosphorylation. Furthermore, we measured adenosine triphosphate (ATP)-levels in the same vascular tissues.
  
  
  RESULTS
  We have found that in rat aortic rings: (1) H(2)S decreases ATP levels; (2) relaxations to H(2)S depend on the ambient oxygen concentration; (3) prostaglandins do not take part in the H(2)S induced relaxations; (4) the 3':5'-cyclic guanosine monophosphate (cGMP)-nitric oxide (NO) pathway does not have a role in the relaxations (5) the role of K(ATP) channels is limited, while Cl(-)/HCO(3)(-) channels have a role in the relaxations. (6): We have observed that high concentrations of H(2)S relax the aortic rings in a fashion similar to sodium cyanide, and both agents reduce cellular ATP levels to a comparable degree.
  
  
  CONCLUSIONS
  H(2)S, a new gasotransmitter of emerging importance, leads to relaxation via Cl(-)/HCO(3)(-) channels and metabolic inhibition and the interactions of these two factors depend on the oxygen levels of the tissue.
authors.affiliation: Department of Surgery, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, University Heights, Newark, NJ 07103-2714, USA.
authors.forename: Levente
authors.initials: L
authors.lastname: Kiss
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D054086:KATP Channels / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010085:Oxidative Phosphorylation; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D054086:KATP Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005905:Glyburide; D006862:Hydrogen Sulfide
references.citation: Br J Pharmacol. 2005 May;145(2):141-4
references.pmid: 15753944
references.citation: Biochem Biophys Res Commun. 2004 Jan 2;313(1):22-7
references.pmid: 14672692
references.citation: Nat Rev Drug Discov. 2007 Nov;6(11):917-35
references.pmid: 17948022
references.citation: Toxicol Appl Pharmacol. 1990 May;103(3):482-90
references.pmid: 2160136
references.citation: Antioxid Redox Signal. 2005 May-Jun;7(5-6):804-12
references.pmid: 15890028
references.citation: Free Radic Biol Med. 2006 Jul 1;41(1):106-19
references.pmid: 16781459
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1930-7
references.pmid: 18417642
references.citation: J Appl Physiol (1985). 2006 Mar;100(3):1065-76
references.pmid: 16467393
references.citation: J Toxicol Environ Health A. 1998 Jul 24;54(6):491-507
references.pmid: 9661914
references.citation: Toxicology. 2007 Nov 20;241(1-2):92-7
references.pmid: 17888559
references.citation: J Physiol. 1997 Sep 1;503 ( Pt 2):333-46
references.pmid: 9306276
references.citation: Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Oct;35(5):488-93
references.pmid: 14601305
references.citation: Biochem Biophys Res Commun. 2006 Jul 7;345(3):938-44
references.pmid: 16707097
references.citation: Med Hypotheses. 2001 Sep;57(3):389-92
references.pmid: 11516234
references.citation: FASEB J. 2005 Apr;19(6):623-5
references.pmid: 15671155
references.citation: Br J Pharmacol. 2006 Nov;149(6):625-34
references.pmid: 17016507
references.citation: Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2316-23
references.pmid: 15191893
references.citation: FASEB J. 2005 Jul;19(9):1196-8
references.pmid: 15863703
references.citation: Shock. 2008 Oct;30(4):359-64
references.pmid: 18323742
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15560-5
references.pmid: 17878306
references.citation: Biochem Biophys Res Commun. 2006 Apr 28;343(1):303-10
references.pmid: 16540095
references.citation: Biochem J. 1984 Dec 1;224(2):591-600
references.pmid: 6097224
references.citation: J Mol Cell Cardiol. 2006 Jan;40(1):119-30
references.pmid: 16325198
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R243-52
references.pmid: 15345473
references.citation: Clin Sci (Lond). 2008 Aug;115(3):91-7
references.pmid: 18315525
references.citation: Am J Physiol. 1991 Mar;260(3 Pt 2):H848-54
references.pmid: 1900392
references.citation: J Physiol. 1990 Apr;423:411-23
references.pmid: 2388156
references.citation: Am J Physiol Heart Circ Physiol. 2007 Apr;292(4):H1953-60
references.pmid: 17237242
references.citation: J Bioenerg Biomembr. 1996 Apr;28(2):207-14
references.pmid: 9132420
references.citation: J Occup Med. 1979 Feb;21(2):93-7
references.pmid: 556262
references.citation: Br J Pharmacol. 2002 Sep;137(2):139-45
references.pmid: 12208769
references.citation: Biochem Biophys Res Commun. 2007 Jul 13;358(4):1142-7
references.pmid: 17531202
references.citation: EMBO J. 2001 Nov 1;20(21):6008-16
references.pmid: 11689441
references.citation: Br J Pharmacol. 2004 Dec;143(7):881-9
references.pmid: 15504752
references.citation: Peptides. 1996;17(8):1373-8
references.pmid: 8971934
references.citation: Biochem Biophys Res Commun. 1997 Aug 28;237(3):527-31
references.pmid: 9299397
references.citation: Circ Res. 1996 Jan;78(1):50-7
references.pmid: 8603505