Angiotensin II-Independent Angiotensin-(1-7) Formation in Rat Hippocampus Involvement of Thimet Oligopeptidase

Autor(es):Mostrar menos -

Pereira, Marilia G. A. G. ^[1] ; Souza, Laura L. ^[1] ; Becari, Christiane ^[2] ; Duarte, Diego A. ^[1] ; Camacho, Fabio R. B. ^[1] ; Oliveira, Jose Antonio C. ^[3] ; Gomes, Marcelo D. ^[1] ; Oliveira, Eduardo B. ^[1] ; Salgado, Maria Cristina O. ^[2] ; Garcia-Cairasco, Norberto ^[3] ; Costa-Neto, Claudio M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem & Immunol, Ribeirao Preto Sch Med, BR-14049 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Sch Med, BR-14049 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Dept Physiol, Ribeirao Preto Sch Med, BR-14049 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Hypertension; v. 62, n. 5, p. 879-885, NOV 2013.
• Citações Web of Science: 13

Resumo

The involvement and relevance of the renin-angiotensin system have been established clearly in cardiovascular diseases, and renin-angiotensin system involvement has also been investigated extensively in the central nervous system. Angiotensin II acts classically by binding to the AT(1) and AT(2) receptors. However, other pathways within the renin-angiotensin system have been described more recently, such as one in which angiotensin-(1-7) (Ang-(1-7)) binds to the receptor Mas. In the central nervous system specifically, it has been reported that this heptapeptide is involved in learning and memory processes that occur in central limbic regions, such as the hippocampus. Therefore, this prompted us to investigate the possible role of the Ang-(1-7)-receptor Mas pathway in epileptic seizures, which are also known to recruit limbic areas. In the present study, we show that Ang-(1-7) is the main metabolite of angiotensin I in rat hippocampi, and, strikingly, that thimet oligopeptidase is the main enzyme involved in the generation of Ang-(1-7). Furthermore, elevations in the levels of thimet oligopeptidase, Ang-(1-7), and of receptor Mas transcripts are observed in chronically stimulated epileptic rats, which suggest that the thimet oligopeptidase-Ang-(1-7)-receptor Mas axis may have a functional relevance in the pathophysiology of these animals. In summary, our data, which describe a new preferential biochemical pathway for the generation of Ang-(1-7) in the central nervous system and an increase in the levels of various elements of the related thimet oligopeptidase-Ang-(1-7)-receptor Mas pathway, unveil potential new roles of the renin-angiotensin system in central nervous system pathophysiology. (AU)

• Processo FAPESP: 07/50261-4 - Neurociências, epilepsia e arte: caracterização interdisciplinar da cepa WAR e modelos de epilepsia correlacionados: as oficinas Da Vinci, divulgação científica e quebras de estigmas em epilepsia
• Beneficiário: Norberto Garcia Cairasco
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/61810-6 - Acões pleiotrópicas dos sistemas renina-angiotensina e calicreínas-cininas
• Beneficiário: Claudio Miguel da Costa Neto
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 02/09406-5 - Regulação neuro-humoral do sistema cardiovascular em condições fisiológicas e fisiopatológicas
• Beneficiário: Maria Cristina de Oliveira Salgado
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 05/56447-7 - Pesquisa através de imagens por ressonância magnética de alto campo destinadas a estudos em humanos
• Beneficiário: João Pereira Leite
• Linha de fomento: Auxílio à Pesquisa - Programa CINAPCE - Temático