Inhibition of the renin-angiotensin system prevents seizures in a rat model of epilepsy

Autor(es)

Pereira, Marilia G. A. G. ^[1] ; Becari, Christiane ^[2] ; Oliveira, Jose A. C. ^[2] ; Salgado, Maria Cristina O. ^[3] ; Garcia-Cairasco, Norberto ^[2] ; Costa-Neto, Claudio M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Science; v. 119, n. 11-12, p. 477-482, DEC 2010.
• Citações Web of Science: 38

Resumo

The RAS (renin angiotensin system) is classically involved in BP (blood pressure) regulation and water electrolyte balance, and in the central nervous system it has been mostly associated with homoeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1-3% of the world's population, and the most commonly used anticonvulsants are described to be effective in approx. 70% of the population with this neurological alteration. Using a rat model of epilepsy, we found that components of the RAS, namely ACE (angiotensin-converting enzyme) and the AT(1) receptor (angiotensin II type I receptor) are up-regulated in the brain (2.6- and 8.2-fold respectively) following repetitive seizures. Subsequently, epileptic animals were treated with clinically used doses of enalapril, an ACE inhibitor, and losartan, an AT(1) receptor blocker, leading to a significant decrease in seizure severities. These results suggest that centrally acting drugs that target the RAS deserve further investigation as possible anticonvulsant agents and may represent an additional strategy in the management of epileptic patients. (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
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Programa CINAPCE - Temático
• Processo FAPESP: 02/09406-5 - Regulação neuro-humoral do sistema cardiovascular em condições fisiológicas e fisiopatológicas
• Beneficiário: Maria Cristina de Oliveira Salgado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/61810-6 - Acões pleiotrópicas dos sistemas renina-angiotensina e calicreínas-cininas
• Beneficiário: Claudio Miguel da Costa Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular