gms | German Medical Science

In a recent study losartan (LOS) shows a dose-dependent antagonistic effect to the endothelin-1 (ET-1) induced vasoconstriction, which could be abolished after preincubation with an endothelin B₁ receptor (ET(B₁)-receptor) antagonist. Also under LOS an increased ET(B₁)-receptor-dependent relaxation to the ET(B)-receptor agonist Sarafotoxin S6c (S6c) was detected. Though, investigations under pathological conditions – like after experimental induced subarachnoid hemorrhage (SAH) – are still missing. Therefore experimental cerebral vasospasm (CVS) was induced by a modified double hemorrhage model. Rats were sacrificed on day 3 and isometric force of basilar artery ring segments was measured. Like under physiological conditions after experimental SAH the ET-1 induced vasoconstriction is decreased under LOS. Interestingly, this reduced vasoconstriction is abolished after preincubation with BQ-788, an ET(B₁)-receptor antagonist. Additionally, in precontracted vessels with BQ-123, an endothelin A-receptor (ET(A)-receptor) antagonist, and LOS ET-1 induced a higher vasorelaxation. After experimental induced SAH LOS causes a modulatory effect in ET(B₁)-receptor-dependent vasorelaxation. LOS further induces an upregulation of the NO-pathway. The formerly known loss of the ET(B₁)-receptor function after SAH was abolished under LOS and a significantly increased relaxation, accompanied with an enhanced sensitivity of the ET(B₁)-receptor, was 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 LOS via the ET(B1)-receptor.