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Neurosurgical Review
Erschienen in: Neurosurgical Review 2/2018

29.07.2017 | Original Article

Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage

verfasst von: Stefan Wanderer, Jan Mrosek, Hartmut Vatter, Volker Seifert, Juergen Konczalla

Erschienen in: Neurosurgical Review | Ausgabe 2/2018

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Abstract

Under physiologic conditions, losartan showed a dose-dependent antagonistic effect to the endothelin-1 (ET-1)-mediated vasoconstriction. This reduced vasoconstriction was abolished after preincubation with an endothelin B1 receptor (ET(B1)-receptor) antagonist. Also, an increased ET(B1)-receptor-dependent relaxation to sarafotoxin S6c (S6c; an ET(B1)-receptor agonist) was detected by preincubation with losartan. Investigations after experimental induced subarachnoid hemorrhage (SAH) are still missing. Therefore, we analyzed losartan in a further pathological setup. Cerebral vasospasm was induced by a modified double hemorrhage model. Rats were sacrificed on day 3 and isometric force of basilar artery ring segments was measured. Parallel to physiological conditions, after SAH, the ET-1-induced vasoconstriction was decreased by preincubation with losartan. This reduced contraction has been abolished after preincubation with BQ-788, an ET(B1)-receptor antagonist. In precontracted vessels, ET-1 induced a higher vasorelaxation under losartan and the endothelin A receptor (ET(A)-receptor) antagonist BQ-123. After SAH, losartan caused a modulatory effect on the ET(B1)-receptor-dependent vasorelaxation. It further induced an upregulation of the NO pathway. Under losartan, the formerly known loss of the ET(B1)-receptor vasomotor function was abolished and a significantly increased relaxation, accompanied with an enhanced sensitivity of the ET(B1)-receptor, has been detected. Also, the dose-dependent antagonistic effect to the ET-1-induced contraction can be effected by angiotensin II type 1 receptor (AT1-receptor) antagonism due to losartan directly via the ET(B1)-receptor.
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Metadaten
Titel
Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage
verfasst von
Stefan Wanderer
Jan Mrosek
Hartmut Vatter
Volker Seifert
Juergen Konczalla
Publikationsdatum
29.07.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Neurosurgical Review / Ausgabe 2/2018
Print ISSN: 0344-5607
Elektronische ISSN: 1437-2320
DOI
https://doi.org/10.1007/s10143-017-0887-z

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