title: Characterization of the endothelin-B receptor expression and vasomotor function during experimental cerebral vasospasm.
abstract: OBJECTIVE
  Several investigations suggest a key role of endothelin (ET) in the development of cerebral vasospasm (CVS). In the cerebrovasculature, physiologically ET-dependent constriction is mediated by the ET(A) receptor, whereas activation of the endothelial ET(B) receptor results in relaxation. However, existence of a contractile ET(B) receptor was postulated after subarachnoid hemorrhage (SAH), according to gene expression studies. The aim of the present investigation is, therefore, to characterize the function and the expression of the ET(B) receptor in the cerebrovasculature during CVS.
  
  
  METHODS
  CVS was induced in the rat double-hemorrhage model and assessed by perfusion-weighted magnetic resonance imaging scans. Rats were sacrificed on Days 3 and 5 after SAH, and immunohistochemical staining for ET(B) receptors was performed. Isometric force of basilar artery ring segments with (E+) and without (E-) endothelial function was measured. Concentration effect curves for the ET(B) receptor agonist, sarafotoxin 6c, were constructed by cumulative application in segments under resting tension and after precontraction.
  
  
  RESULTS
  Immunoreactivity for the ET(B) receptor was observed exclusively in the endothelium and was not significantly altered after SAH. Under resting tension, sarafotoxin 6c did not induce significant contraction in E+ or E- segments. After precontraction, a significant relaxation was induced by sarafotoxin 6c administration in sham-operated rats (mean maximum effect, 103 +/- 10%), which decreased time dependently after SAH (Day 3, 68 +/- 3%; Day 5, 42 +/- 3%). Endothelium-dependent relaxation induced by acetylcholine, however, was not significantly reduced.
  
  
  CONCLUSIONS
  The present investigation provides evidence for the loss of the ET(B) receptor-mediated vasomotor function after SAH. Thus, antagonism of the ET(B) receptor may be undesirable for the treatment of CVS.
authors.affiliation: Department of Neurosurgery, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. H.Vatter@em.uni-frankfurt.de
authors.forename: Hartmut
authors.initials: H
authors.lastname: Vatter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Konczalla
authors.forename: Stefan
authors.initials: S
authors.lastname: Weidauer
authors.forename: Christine
authors.initials: C
authors.lastname: Preibisch
authors.forename: Andreas
authors.initials: A
authors.lastname: Raabe
authors.forename: Michael
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Volker
authors.initials: V
authors.lastname: Seifert
mesh_terms: D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000150:complications; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014666:Vasomotor System / Q000503:physiopathology; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D044023:Receptor, Endothelin B