title: The levels of renin-angiotensin related components are modified in the hippocampus of rats submitted to pilocarpine model of epilepsy.
abstract: We previously showed that patients with temporal lobe epilepsy (TLE) present an increased expression of angiotensin II (AngII) AT1 and AT2 receptors in the hippocampus, supporting the idea of an upregulation of renin-angiotensin system (RAS) in this disease. This study aimed to verify the relationship between the RAS and TLE during epileptogenesis. Levels of the peptides angiotensin I (AngI), angiotensin II (AngII) and angiotensin 1-7 (Ang 1-7), were detected by HPLC assay. Angiotensin AT1 and AT2 receptors, Mas mRNA receptors and angiotensin converting enzyme (ACE), tonin and neutral endopeptidase (NEP) mRNA were also quantified at the hippocampus of Wistar rats by real time PCR, during acute (n=10), silent (n=10) and chronic (n=10) phases of pilocarpine-induced epilepsy. We observed an increased peptide level of Ang1-7 into acute and silent phases, decreasing importantly (p≤0.05) in the chronic phase, suggesting that AngI may be converted into Ang 1-7 by NEP, which is present in high levels in these periods. Our results also showed increased peptide level of AngII in the chronic phase of this model. In contraposition, the ACE expression is reduced in all periods. These data suggest that angiotensinogen or AngI may be cleaved to AngII by tonin, which showed increased expression in all phases. We found changes in AT1, AT2 and Mas mRNA receptors levels suggesting that Ang1-7 could act at Mas receptor during the silent period. Herein, we demonstrated for the first time, changes in angiotensin-related peptides, their receptors as well as the releasing enzymes in the hippocampus of rats during pilocarpine-induced epilepsy.
authors.affiliation: Neurology and Neurosurgery Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Telma Luciana Furtado
authors.initials: TL
authors.lastname: Gouveia
authors.forename: Maria Isabel Berzaghi
authors.initials: MI
authors.lastname: Frangiotti
authors.forename: Joíse Marques Vieira
authors.initials: JM
authors.lastname: de Brito
authors.forename: Eduardo Ferreira
authors.initials: EF
authors.lastname: de Castro Neto
authors.forename: Maisa Mayume
authors.initials: MM
authors.lastname: Sakata
authors.forename: Andreia Cristina
authors.initials: AC
authors.lastname: Febba
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
authors.forename: Débora
authors.initials: D
authors.lastname: Amado
authors.forename: Esper Abrão
authors.initials: EA
authors.lastname: Cavalheiro
authors.forename: Sandro Soares
authors.initials: SS
authors.lastname: Almeida
authors.forename: Martha Trindade
authors.initials: MT
authors.lastname: Manchini
authors.forename: Ronaldo Carvalho
authors.initials: RC
authors.lastname: Araújo
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Silva
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Naffah-Mazzacoratti
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012084:Renin-Angiotensin System
chemical_list: D017931:DNA Primers; D010862:Pilocarpine