title: The effect of endothelin receptor A antagonism on basilar artery endothelium-dependent relaxation after ischemic stroke.
abstract: OBJECTIVE
  Endothelin (ET) receptor A antagonism decreases neuronal damage in experimental models of stroke. Since large arteries like basilar artery contribute significantly to total cerebrovascular resistance and are major determinants of microvascular pressure, dysregulation of basilar artery function may worsen stroke injury. ET-1 is involved in the regulation of basilar constriction. However, whether stroke influences vasoreactivity of basilar artery and to what extent ET-1 contributes to basilar vascular dysfunction after stroke remained unknown. The goal of this study was to test the hypothesis that ET-1 impairs basilar artery vasorelaxation after ischemia/reperfusion (I/R) injury via activation of ET(A) receptor.
  
  
  METHODS
  Male Wistar rats were subjected to 3h middle cerebral artery occlusion (MCAO) and 21 h reperfusion. One group received ET(A) receptor antagonist atrasentan (5 mg/kg, i.p.) at reperfusion. At 24h, basilar arteries were isolated from control non-stroked, stroked and stroked+atrasentan-treated animals for vascular reactivity measurements using pressurized arteriograph.
  
  
  RESULTS
  Acetylcholine (Ach)-induced maximum relaxation (R(max)) was decreased in stroked animals as compared to non-stroked group and ET(A) antagonism partially restored it. There was also a trend for decreased EC(50) value for the antagonist treatment group indicating improved Ach sensitivity.
  
  
  CONCLUSIONS
  These findings suggest that I/R not only affects vessels distal to the occlusion but also impairs relaxation of proximal large vessels. ET-1-mediated basilar artery dysfunction may contribute to neurovascular damage after stroke and early restoration of vascular function by ET receptor antagonism after I/R injury may offer a therapeutic strategy.
authors.affiliation: Department of Physiology, Georgia Health Sciences University, Augusta, GA 30912, United States.
authors.forename: Maha
authors.initials: M
authors.lastname: Coucha
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000077868:Atrasentan; D001488:Basilar Artery / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D020521:Stroke / Q000188:drug therapy / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D000109:Acetylcholine; D000077868:Atrasentan