Back
Crosstalk between the angiotensin and endothelin system in the cerebrovasculature after experimental induced subarachnoid hemorrhage.
Journal article

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

  • Wanderer S Department of Neurosurgery, Kantonsspital Aarau, Aarau, Switzerland. stefan.wanderer@ksa.ch.
  • Mrosek J Department of Neurosurgery, Goethe-University Hospital, Frankfurt am Main, Germany.
  • Vatter H Department of Neurosurgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
  • Seifert V Department of Neurosurgery, Goethe-University Hospital, Frankfurt am Main, Germany.
  • Konczalla J Department of Neurosurgery, Goethe-University Hospital, Frankfurt am Main, Germany.
  • 2017-07-31
Published in:
  • Neurosurgical review. - 2018
AT1-receptor
Angiotensin
Cerebrovasculature
Crosstalk
ET(A)-receptor
ET(B1)-receptor
Endothelin
Losartan
Subarachnoid hemorrhage
Angiotensin II Type 1 Receptor Blockers
Angiotensins
Animals
Basilar Artery
Disease Models, Animal
Endothelin Receptor Antagonists
Endothelin-1
Losartan
Male
Oligopeptides
Peptides, Cyclic
Piperidines
Rats
Rats, Sprague-Dawley
Receptor Cross-Talk
Subarachnoid Hemorrhage
Vasoconstriction
Vasodilation
Vasospasm, Intracranial
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/186307
Statistics
Document views: 34 File downloads: