Angiotensin-converting enzyme inhibition, angiotensin, and cognition.
In these studies, we have investigated possible cognition-enhancing effects of angiotensin-converting enzyme (ACE) inhibition, and putative neurochemical correlates for these actions. In a mouse habituation model, ACE inhibitors improved basal performance and antagonized scopolamine-induced deficits. The performance of aged mice and those with lesions of the nucleus basalis was also improved. ACE inhibition also improved scopolamine-impaired performance of rats in a swim-maze model. Neurochemical studies showed that a low dose (10 micrograms/kg i.p.) of ceranapril caused significant alterations in ex vivo rat brain catecholamine levels in the nucleus accumbens, amygdala, and septum. In further studies, angiotensin II (Ang II) was shown to decrease potassium-stimulated [3H] acetylcholine release from slices of rat entorhinal and human temporal cortex, an effect that could be antagonized by the angiotensin receptor antagonist [1-sar,8-thr]Ang II. It is concluded that ACE inhibition can improve both basal and impaired performance in animal models of learning, and that this improvement may be in part a consequence of the removal by ACE inhibition of an inhibitory tone on central acetylcholine release, and/or an effect on central catecholaminergic function.
Barnes
J M
JM
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, W. Yorks, England.
Barnes
N M
NM
Costall
B
B
Coughlan
J
J
Kelly
M E
ME
Naylor
R J
RJ
Tomkins
D M
DM
Williams
T J
TJ
D000109:Acetylcholine / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D009943:Organophosphorus Compounds; D000804:Angiotensin II; D011392:Proline; D012601:Scopolamine; D000109:Acetylcholine; D011188:Potassium; C054518:ceronapril