title: Interleukin-1 beta rapidly inhibits aortic endothelium-dependent relaxation by a DNA transcription-dependent mechanism.
abstract: OBJECTIVE
  This study examined the effects of interleukin-1 beta on isometric tension development and relaxation in isolated rat aortic rings in response to the alpha-1 adrenergic agonist phenylephrine, the endothelium-dependent vasodilator acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside.
  
  
  METHODS
  Randomized, controlled, paired design.
  
  
  METHODS
  Animal laboratory within a university department of physiology. SUBJECTS Paired aortic thoracic aortic rings from specific pathogen-free Sprague-Dawley rats.
  
  
  METHODS
  Series I examined the potential for interleukin-1 beta to cause early arterial endothelial dysfunction. Paired aortic rings were incubated for 2 hrs with interleukin-1 beta or vehicle. Series II examined the potential for inhibition of DNA transcription to attenuate interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin or vehicle before interleukin-1 beta incubation. Series III quantified the degree to which inhibition of DNA transcription inhibited early interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin pretreatment followed by interleukin-1 beta incubation, or pretreatment and incubation with inert vehicles. Series IV assessed the effects of interleukin-1 beta on responsiveness to an exogenous nitric oxide donor, sodium nitroprusside, in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester.
  
  
  RESULTS
  Incubation with interleukin-1 beta for 2 hrs had no effect on contractile response but attenuated endothelium-dependent relaxation significantly relative to control. Dactinomycin pretreatment inhibited early interleukin-1 beta-mediated endothelial dysfunction. The combination of interleukin-1 beta and dactinomycin produced effects on endothelium-dependent relaxation that were not different from that seen in rings not exposed to interleukin-1 beta. Interleukin-1 beta attenuated responsiveness to sodium nitroprusside relative to control.
  
  
  CONCLUSIONS
  Interleukin-1 beta causes an early impairment of endothelium-dependent vasorelaxation with an onset that precedes its effects on systemic contractility. This impairment occurs via a mechanism that is wholly or predominantly dependent on DNA transcription. The altered vasorelaxation induced by interleukin-1 beta is at least partly mediated by a reduction in nitric oxide responsiveness.
authors.affiliation: Department of Anaesthesia, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: J P R
authors.initials: JP
authors.lastname: Loughrey
authors.forename: J G
authors.initials: JG
authors.lastname: Laffey
authors.forename: B J
authors.initials: BJ
authors.lastname: Moore
authors.forename: F
authors.initials: F
authors.lastname: Lynch
authors.forename: J F
authors.initials: JF
authors.lastname: Boylan
authors.forename: P
authors.initials: P
authors.lastname: McLoughlin
mesh_terms: D000109:Acetylcholine / Q000276:immunology / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D004247:DNA; D003609:Dactinomycin / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000276:immunology / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000276:immunology / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000276:immunology*; D014665:Vasodilator Agents / Q000276:immunology / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D007375:Interleukin-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D003609:Dactinomycin; D010656:Phenylephrine; D004247:DNA; D000109:Acetylcholine