title: Crosstalk between the angiotensin and endothelin-system in the cerebrovasculature.
abstract: Investigations have shown a multifactorial process as cause for the poor outcome after subarachnoid hemorrhage (SAH), including inflammation, early brain injury, cortical spreading depression, lack of cerebral autoregulation and the cerebral vasospasm (CVS) itself. Losartan may have a beneficial effect after SAH - preventing CVS, restoring cerebral autoregulation, reducing inflammation and early brain injury. Also some data is available for an AT1-receptor-upregulation and upregulated gene expression after subarachnoid hemorrhage, but the functional role of angiotensin on the cerebrovascular contractility is still not completely understood. Therefore, the aim of the present investigation was to detect functional interactions between the AT1-receptor blockade (by losartan) and the endothelin-1 (ET-1) dependent vasoconstriction and vasorelaxation in the basilar artery. To investigate the functional role of losartan on rat's basilar artery, changes of the vasoreactivity in an organ bath were determined. Under losartan the ET-1 induced contraction is decreased. After incubation with BQ-788, an ET(B)-receptor antagonist, the lowered contraction is abolished. In precontracted vessels under losartan and BQ-123, an ET(A)-receptor antagonist, ET-1 induced a higher relaxation. AT1-receptor antagonism causes a modulatory effect in ET(B)-receptor-dependent vasorelaxation in the basilar artery. AT1-receptor antagonism due to losartan induces the upregulation of the NO-pathway with a significantly increased relaxation accompanied with enhanced sensitivity of the ET(B)-receptor. Losartan has a dose-dependent antagonistic effect to the ET-1 induced contraction, which seems to ET(B)-receptor dependent. This antagonistic effect could be another beneficial effect after subarachnoid hemorrhage, additionally to the known effects after stroke: preventing CVS, restoring cerebral autoregulation, reducing inflammation and early brain injury.
authors.affiliation: Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main, Schleusenweg 2- 16, 60528 Frankfurt am Main, Germany. J.Konczalla@med.uni-frankfurt.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Konczalla
authors.forename: Stefan
authors.initials: S
authors.lastname: Wanderer
authors.forename: Jan
authors.initials: J
authors.lastname: Mrosek
authors.forename: Patrick
authors.initials: P
authors.lastname: Schuss
authors.forename: Johannes
authors.initials: J
authors.lastname: Platz
authors.forename: Erdem
authors.initials: E
authors.lastname: Güresir
authors.forename: Volker
authors.initials: V
authors.lastname: Seifert
authors.forename: Hartmut
authors.initials: H
authors.lastname: Vatter
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication; D019332:Endothelin-1 / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000378:metabolism / Q000503:physiopathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D019332:Endothelin-1; D019808:Losartan