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
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