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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 11
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Hypertension; v. 62, n. 5, p. 879-885, NOV 2013.
Web of Science Citations: 14
Abstract

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)

FAPESP's process: 05/56447-7 - Research through images from high field magnetic resonance aimed at studies in humans
Grantee:João Pereira Leite
Support Opportunities: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants
FAPESP's process: 02/09406-5 - Neuro-humoral regulation of the cadiovascular system in physiological and physiopathological conditions
Grantee:Maria Cristina de Oliveira Salgado
Support Opportunities: Research Projects - Thematic Grants