title: Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice.
abstract: OBJECTIVE
  Hydrogen sulphide (H2S) has been involved in cardiovascular homoeostasis but data about its role in animal models of diabetic pathology are still lacking. Here, we have analysed H2S signalling in a genetic model of diabetes, the non-obese diabetic (NOD) mice.
  
  
  METHODS
  NOD mice exhibit a progressive endothelial dysfunction characterized by a reduced reactivity of blood vessels as diabetes develops. NOD mice were divided into three groups according to different glycosuria values: NOD I, NOD II and NOD III. Age-matched non-obese resistant (NOR) mice were used as controls. H(2)S levels in plasma and aortic tissue were measured. Functional studies in aorta were carried out in isolated organ baths using both an exogenous source of H2S (NaHS) and the metabolic precursor (L-cysteine). Real time PCR and western blot analysis were also carried out on aortic tissues.
  
  
  RESULTS
  NOD mice exhibited a progressive reduction of H2S plasma levels, which paralleled disease severity. L-cysteine-induced H2S production by aortic tissues was also progressively reduced. L-cysteine-induced vasorelaxation was significantly reduced in NOD mice while NaHS-induced relaxation was unaffected. ODQ (guanylate cyclase inhibitor), L-NAME (NO synthase inhibitor) or PAG, an inhibitor of cystathionine-gamma-lyase (CSE) inhibited H2S production induced by L-cysteine.
  
  
  CONCLUSIONS
  In NOD mice, endogenous H2S production is significantly impaired. Also, the ability of isolated aorta to respond to exogenous H2S is enhanced and endothelium-derived NO appears to be involved in the enzymatic conversion of L-cysteine into H2S.
authors.affiliation: Department of Experimental Pharmacology, University of Naples, Naples, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Brancaleone
authors.forename: F
authors.initials: F
authors.lastname: Roviezzo
authors.forename: V
authors.initials: V
authors.lastname: Vellecco
authors.forename: L
authors.initials: L
authors.lastname: De Gruttola
authors.forename: M
authors.initials: M
authors.lastname: Bucci
authors.forename: G
authors.initials: G
authors.lastname: Cirino
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester; D006862:Hydrogen Sulfide