title: Detrimental effects of nitric oxide on mesenteric circulation during endotoxaemia and its reversal by aminoguanidine.
abstract: OBJECTIVE
  To investigate the effect of endotoxaemia on rat mesenteric vascular bed and plasma nitrite concentrations, the possible beneficial effect of aminoguanidine (the selective inducible nitric oxide synthase inhibitor) compared with N(G)-nitro-L-arginine methyl ester (L-NAME) (non-selective nitric oxide synthase inhibitor).
  
  
  METHODS
  Randomised experiment.
  
  
  METHODS
  University surgical research laboratory, Turkey.
  
  
  METHODS
  75 Wistar rats.
  
  
  METHODS
  Rats were divided into control (n = 30) and endotoxaemia (n = 42) groups. Endotoxaemia was produced by intraperitoneal injection of lipopolysaccharide 20 mg/kg. Subgroups were given either aminoguanidine or L-NAME.
  
  
  METHODS
  After 4 hours, isolated perfused mesenteric preparations were obtained and pressor responses to phenylephrine and vasodilatation responses to acetylcholine were evaluated, and plasma nitrite concentrations measured.
  
  
  RESULTS
  Pressor response to phenylephrine did not alter but vasodilatation in response to acetylcholine was significantly reduced during endotoxaemia. Pretreatment with aminoguanidine prevented the impairment of the response to acetylcholine. However, L-NAME was ineffective. In the control group, aminoguanidine and L-NAME did not alter the vascular reactivity. The baseline plasma nitrite concentrations in the control group were increased 5-fold during endotoxaemia. This increase was significantly reduced with aminoguanidine but not with L-NAME.
  
  
  CONCLUSIONS
  The protection achieved by aminoguanidine but not L-NAME suggested that nitric oxide produced by inducible nitric oxide synthase had a role in the impairment of endothelial response during endotoxaemia, and confirmed the importance of selective inducible nitric oxide synthase inhibition to achieve beneficial effects in endotoxaemia.
authors.affiliation: Department of General Surgery, Hacettepe University, Ankara, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Yorganci
authors.forename: I
authors.initials: I
authors.lastname: Sayek
authors.forename: U B
authors.initials: UB
authors.lastname: Ismailoglu
authors.forename: I
authors.initials: I
authors.lastname: Sahin-Erdemli
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D003627:Data Interpretation, Statistical; D019446:Endotoxemia / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008643:Mesentery / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000097:blood*; D010656:Phenylephrine / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009573:Nitrites; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester