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- Title
Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage.
- Authors
Wanderer, Stefan; Mrosek, Jan; Seifert, Volker; Konczalla, Juergen; Vatter, Hartmut
- 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.
- Subjects
SUBARACHNOID hemorrhage; CEREBROVASCULAR disease; ENDOTHELINS regulation; ANGIOTENSINS; LOSARTAN; BIOLOGICAL crosstalk; THERAPEUTICS
- Publication
Neurosurgical Review, 2018, Vol 41, Issue 2, p539
- ISSN
0344-5607
- Publication type
Article
- DOI
10.1007/s10143-017-0887-z