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01-04-2018 | Original Article

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

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

Published in: Neurosurgical Review | Issue 2/2018

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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Title: Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage
Authors: Stefan Wanderer
Jan Mrosek
Hartmut Vatter
Volker Seifert
Juergen Konczalla
Publication date: 01-04-2018
Publisher: Springer Berlin Heidelberg
Published in: Neurosurgical Review / Issue 2/2018
Print ISSN: 0344-5607
Electronic ISSN: 1437-2320
DOI: https://doi.org/10.1007/s10143-017-0887-z

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

Abstract

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Abstract

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