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 AT1 receptor (angiotensin II type 1 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 AT1 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.
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December 2010
Research Article|
August 17 2010
Inhibition of the renin–angiotensin system prevents seizures in a rat model of epilepsy
Marilia G.A.G. Pereira
;
Marilia G.A.G. Pereira
1
*Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
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Christiane Becari
;
Christiane Becari
1
†Department of Pharmacology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
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José A.C. Oliveira
;
José A.C. Oliveira
‡Department of Physiology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
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Maria Cristina O. Salgado
;
†Department of Pharmacology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
Correspondence: Professor Claudio M. Costa-Neto (email claudio@fmrp.usp.br), Dr Norberto Garcia-Cairasco (email ngcairas@fmrp.usp.br) or Dr Maria Cristina O. Salgado (email mcdosalg@fmrp.usp.br).
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Norberto Garcia-Cairasco
;
‡Department of Physiology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
Correspondence: Professor Claudio M. Costa-Neto (email claudio@fmrp.usp.br), Dr Norberto Garcia-Cairasco (email ngcairas@fmrp.usp.br) or Dr Maria Cristina O. Salgado (email mcdosalg@fmrp.usp.br).
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Claudio M. Costa-Neto
*Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil
Correspondence: Professor Claudio M. Costa-Neto (email claudio@fmrp.usp.br), Dr Norberto Garcia-Cairasco (email ngcairas@fmrp.usp.br) or Dr Maria Cristina O. Salgado (email mcdosalg@fmrp.usp.br).
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Clin Sci (Lond) (2010) 119 (11): 477–482.
Article history
Received:
January 22 2010
Revision Received:
June 02 2010
Accepted:
June 10 2010
Accepted Manuscript online:
June 10 2010
Citation
Marilia G.A.G. Pereira, Christiane Becari, José A.C. Oliveira, Maria Cristina O. Salgado, Norberto Garcia-Cairasco, Claudio M. Costa-Neto; Inhibition of the renin–angiotensin system prevents seizures in a rat model of epilepsy. Clin Sci (Lond) 1 December 2010; 119 (11): 477–482. doi: https://doi.org/10.1042/CS20100053
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