The Effect of Losartan on Neuroinflammation as Well as on Endothelin-1- and Serotonin-Induced Vasoconstriction in a Double-Haemorrhage Rat Model

Abstract

Poor patient outcome after aneurysmal subarachnoid haemorrhage (SAH) is due to a multifactorial process. Delayed cerebral vasospasm, ischemic neurological deficits, and infarction are the most feared acute sequelae triggered by enhanced synthesis of serotonin and endothelin-1 (ET-1). During the past decades, multiple drugs have been analysed for protective effects without resounding success. Therefore, the authors wanted to analyse the potential beneficial role of Losartan (LOS). Male Sprague Dawley rats were randomised into either a group receiving two injections of blood into the cisterna magna (SAH group) or a group receiving two injections of isotonic sodium chloride (sham group). The animals were culled on day five and basilar artery ring segments were used for in vitro tension studies. Sarafotoxin S6c caused a dose-dependent vasorelaxation in sham and SAH segments, which was more pronounced in sham segments. LOS, applied in a concentration of 10−3 M, was able to significantly reduce serotonin- (p < 0.01) and ET-1- (p < 0.05, p < 0.01) mediated vasoconstriction in sham segments. These findings, along with the well-known beneficial effects of LOS on restoring the impaired endothelin-B1-receptor function after SAH, as well as on the neuroprotectional and antiepileptogenic aspects, might be implemented in advancing tailored concepts to sufficiently ameliorate patients’ functional outcome after SAH.