Angiotensin II blockade of long-term potentiation at the perforant path--granule cell synapse in vitro.

Field recordings of evoked excitatory postsynaptic potentials (pEPSPs) were carried out in the granule cell stratum moleculare following stimulation of the perforant path in rat hippocampal slices. Under control conditions tetanic stimulation produced long-term potentiation (LTP) as measured by an increase in the initial slope of the pEPSPs that lasted for at least 1 h. LTP experiments were repeated with 0.5, 5.0, 50, or 500 nM angiotensin II (AII) present in the bath at the time of tetanization. Induction of LTP was blocked by 50 nM AII; however, normal baseline responses were not affected. At the highest dose tested, 500 nM, a decrease in the amplitude and slope of baseline pEPSPs was observed. When the AII AT1 receptor antagonist losartan was present in the bath AII inhibition of LTP was blocked. The application of losartan alone had no effect on LTP expression. These findings support previous results from in vivo studies demonstrating that activation of AT1 receptors in the dentate gyrus blocks the induction of LTP at the perforant path-granule cell synapse.