Role of angiotensin II and AT1 receptors in hippocampal LTP

Pharmacology, Biochemistry, and Behavior
M J WaynerJ B Denny

Abstract

Results of a previous study showed that angiotensin II (AII) inhibited the induction of long-term potentiation (LTP) in hippocampal granule cells in response to dorsomedial perforant path stimulation in urethane-anesthetized rats. The results of present experiments demonstrate a dose-dependent inhibition of LTP induction under the same conditions due to ethanol (EtOH) administered by stomach tube and diazepam (DZ) injected IP. The inhibition of LTP induction by EtOH and DZ can be blocked by saralasin (SAR) applied directly to the dorsal hippocampus and by lorsartan (DuP 753) administered IP. Lorsartan or a metabolite crosses the blood-brain barrier because it also blocks the inhibition of LTP induction due to AII administration directly into the dorsal hippocampus. Lorsartan is a competitive antagonist of the AT1 subtype AII receptor. Therefore, the AII and the EtOH and DZ inhibition of LTP induction are mediated by the AII subtype receptor AT1. AIII and the AT2 antagonist PD123319 did not produce any significant effects. These in vivo effects can be reproduced in brain slices and therefore cannot be attributed to other factors, such as the urethane. In addition, electrical stimulation of the lateral hypothalamus (LH) inhibits ...Continue Reading

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