Inhibition of the renin-angiotensin system prevents seizures in a rat model of epilepsy.
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.
Department of Biochemistry and Immunology, Faculty of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, Brazil.
Marilia G A G
MG
Pereira
Christiane
C
Becari
José A C
JA
Oliveira
Maria Cristina O
MC
Salgado
Norberto
N
Garcia-Cairasco
Claudio M
CM
Costa-Neto
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000927:Anticonvulsants; D044140:Receptor, Angiotensin, Type 1; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan