title: Permanent distal occlusion of middle cerebral artery in rat causes local increased ETB, 5-HT₁B and AT₁ receptor-mediated contractility downstream of occlusion.
abstract: OBJECTIVE
  In response to experimental stroke, a characteristic functional and expressional upregulation of contractile G-protein-coupled receptors has been uncovered in the affected cerebral vasculature; however, the mechanism initiating this phenomenon remains unknown.
  
  
  METHODS
  Using a model of permanent distal occlusion of rat middle cerebral arteries, we investigated whether there was a regional difference in receptor-mediated contractility of segments located upstream and downstream of the occlusion site. The contractile response to endothelin, angiotensin and 5-hydroxytryptamine receptor stimulation was studied by sensitive wire myograph.
  
  
  RESULTS
  Only downstream segments exhibited an augmented contractile response to stimulation with each of the three ligands, with the response towards sarafotoxin 6c being especially augmented compared to sham, upstream and contralateral controls. This functional increase did not seem to relate to ischemic tissue damage, inflammatory cell infiltration or the element of reperfusion. Interestingly, immunohistochemistry did not show any difference in the level of immunoreactivity towards endothelin B (ETB) receptors between groups.
  
  
  CONCLUSIONS
  Single artery occlusion without significant visible infarct resulted in locally increased ETB, angiotensin type 1 and 5-hydroxytryptamine 1B receptor-mediated contractile responses only in segments located downstream of the occlusion site. This suggests lack of wall stress as an initiating trigger leading to regulation of contractile response after cerebral stroke.
authors.affiliation: Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup University Hospital, Glostrup, Denmark.
authors.forename: Marianne N P
authors.initials: MN
authors.lastname: Rasmussen
authors.forename: Malene
authors.initials: M
authors.lastname: Hornbak
authors.forename: Stine S
authors.initials: SS
authors.lastname: Larsen
authors.forename: Majid
authors.initials: M
authors.lastname: Sheykhzade
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009213:Myography; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D020521:Stroke / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044023:Receptor, Endothelin B; D044302:Receptor, Serotonin, 5-HT1B; D014757:Viper Venoms; C057354:sarafotoxins s6