Angiotensin II Inhibits Cortical Cholinergic Function

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Abstract
In the present studies we have shown that angiotensin II (AT II), in a concentration-dependent manner in rat tissue (10−9-10−5M) or at a single concentration in human tissue (10−6M), can inhibit potassium-stimulated release of [3H]acetylcholine ([3H]Ach) from slices of rat entorhinal cortex and human temporal cortex preloaded with [3H]choline for the biochemical analyses. The inhibitory effects of AT II (10−6M) were antagonised by the specific AT II receptor antagonist [1-sarcosine,8-threonine]AT II in a concentration-dependent manner in rat tissue (10−11 −10−8M) and at the single concentration employed in the human studies (10−7M). Also demonstrated were other components of the angiotensin system in the human temporal cortex; ACE activity was present (1.03 nmol min−1 mg−1 protein), as were AT II recognition sites (Bmax = 8.6 fmol mg−1 protein). It is hypothesised that the potential cognitive enhancing properties of ACE inhibitors may reflect their action to prevent the formation of AT II and so remove an inhibitory modulator of cholinergic function.