title: Cerebral ischemia upregulates vascular endothelin ET(B) receptors in rat.
abstract: OBJECTIVE
  Elevated levels of endothelin-1 (ET-1) have been reported in cerebral ischemia. A role for ET may prove more important if the vascular receptors were changed. We addressed whether there is any change in ET receptor expression in cerebral ischemia.
  
  
  METHODS
  The right middle cerebral artery (MCA) was occluded in male Wistar rats for 2 hours with the intraluminal filament method. The basilar artery and both MCAs were removed after 46 hours of recirculation. The contractile responses to ET-1, a combined ET(A) and ET(B) receptor agonist, and sarafotoxin 6c (S6c), a selective ET(B) receptor agonist, were examined in vitro, and ET receptor mRNA was quantified by real-time polymerase chain reaction.
  
  
  RESULTS
  S6c, which had no contractile effect per se on fresh or sham-operated rat cerebral arteries, induced a marked contraction in the occluded MCA (E(max) [maximum contraction, calculated as percentage of the contractile capacity of 63.5 mmol/L K+]=68+/-68%; P<0.0001), while there was no difference in the responses to ET-1 after cerebral ischemia. Real-time polymerase chain reaction revealed a significant upregulation of both the ET(A) and ET(B) receptors (both P<0.05) in the occluded MCA compared with the nonoccluded MCA from the same rats.
  
  
  CONCLUSIONS
  Focal cerebral ischemia in rat induces increased transcription of both ET(A) and ET(B) receptors, which results in the appearance of a contractile response to the ET(B) receptor agonist S6c. These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia.
authors.affiliation: Division of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, Lund, Sweden. Emelie.Stenman@med.lu.se
authors.forename: Emelie
authors.initials: E
authors.lastname: Stenman
authors.forename: Malin
authors.initials: M
authors.lastname: Malmsjö
authors.forename: Erik
authors.initials: E
authors.lastname: Uddman
authors.forename: Gunilla
authors.initials: G
authors.lastname: Gidö
authors.forename: Tadeuz
authors.initials: T
authors.lastname: Wieloch
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000503:physiopathology; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6