INTRODUCTION: Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II type 1 receptor blockers (ARBs) possess antihypertensive and neuroprotective properties. Kynurenic acid (KYNA), a broad spectrum glutamate antagonist is produced from L-kynurenine by kynurenine aminotransferases (KAT), mainly by KAT I and KAT II isoforms. AIM(S): The goal of our study was to analyze the effect of ACE-Is and ARBs on KYNA synthesis and KATs activity in rat brain cortex in vitro. METHOD(S): The influence of ACE‑Is (lisinopril, perindopril and ramipril) and ARBs (irbesartan, losartan, telmisartan) on KYNA production and KATs activity was examined. Slices and homogenates of rat brain cortex were incubated for 2 hours in the presence of L-kynurenine and examined ACE-I or ARB. KYNA was separated by HPLC and quantified fluorometrically. Moreover, the molecular docking of ARBs to KAT II and the analysis of KAT II coding genes expression in human and rat cerebral cortex were performed. RESULTS: ACE‑Is differently influenced KYNA synthesis and KATs activity in rat brain cortex in vitro. All examined ARBs decreased KYNA production and both KAT I and KAT II activity in rat brain cortex in vitro. Molecular docking showed that analyzed ARBs can bind to an active site of KAT II. CONCLUSIONS: Our study indicates that ACE-Is and ARBs may change KYNA production in rat brain cortex in vitro. ARBs inhibitory effect on KATs activity and KYNA synthesis suggest that ARBs may have beneficial effect in schizophrenia or dementia. FINANCIAL SUPPORT: This study was supported by National Science Centre (NCN) grant PRELUDIUM 4, No UMO-2012/07/N/NZ4/02088.
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