title: Increased endothelin-1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia-reperfusion.
abstract: OBJECTIVE
  Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1.
  
  
  METHODS
  SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O(2) (•-) ) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively.
  
  
  RESULTS
  I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ET(B) mRNA expression, and down-regulated ET(A) mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ET(B) receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ET(B) receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ET(B) receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, N(ω) -nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O(2) (•-) production by increasing NADPH oxidase 1 (NOX-1) and p(47phox) mRNA.
  
  
  CONCLUSIONS
  Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ET(B) receptors and decrease in NO bioavailability.
authors.affiliation: Departament de Farmacologia, Terapèutica i Toxicologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Martínez-Revelles
authors.forename: L
authors.initials: L
authors.lastname: Caracuel
authors.forename: A
authors.initials: A
authors.lastname: Márquez-Martín
authors.forename: Ap
authors.initials: A
authors.lastname: Dantas
authors.forename: E
authors.initials: E
authors.lastname: Oliver
authors.forename: P
authors.initials: P
authors.lastname: D'Ocon
authors.forename: E
authors.initials: E
authors.lastname: Vila
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology; D015424:Reperfusion; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin