ANGIOTENSIN-II INHIBITS CORTICAL CHOLINERGIC FUNCTION - IMPLICATIONS FOR COGNITION

In the present studies we have shown that angiotensin II (AT II), in a concentration-dependent manner in rat tissue (10-9-10-5 M) or at a single concentration in human tissue (10-6 M), 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 (10-6 M) 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 -10-8 M) and at the single concentration employed in the human studies (10-7 M). 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. © 1990 Raven Press, Ltd., New York.