Non-AT1-receptor-mediated protective effect of angiotensin against acute ischaemic stroke in the gerbil

Abstract

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang II is blood pressure (BP)-independent,1 and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I), enalapril, decreases mortality following unilateral carotid artery ligation.2 The aim of this study was to examine the reproducibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils by unilateral carotid ligation. The effect of pretreatment with two different ACE-I (enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed by a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.