AUTHOR=Becari Christiane , Pereira Giorgia Lemes , Oliveira José A. C. , Polonis Katarzyna , Garcia-Cairasco Norberto , Costa-Neto Claudio M. , Pereira Marilia G. A. G. 

TITLE=Epilepsy Seizures in Spontaneously Hypertensive Rats After Acoustic Stimulation: Role of Renin–Angiotensin System

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.588477

DOI=10.3389/fnins.2020.588477

ISSN=1662-453X

ABSTRACT=Hypertension is a common comorbidity observed in epileptic individuals. Growing evidence suggests that lower blood pressure is associated with reduced frequency and severity of seizures. In this study, we sought to investigate whether the renin-angiotensin system (RAS), which is a critical regulator of blood pressure, is involved in the pathogenesis of epilepsy-related seizures in a rat model. Spontaneously hypertensive rats (SHRs) were given RAS inhibitors: angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type I receptor (AT1R) antagonist for 7 days prior to inducing epileptic seizures by audiogenic stimulation. After the pre-treatment phase, blood pressure (BP) of SHRs normalized as expected and there was no difference in systolic and diastolic BP between the pre-treated SHRs and normotensive rat group (Wistar). Next, treated and untreated SHRs (a high BP control) were individually subjected to audiogenic stimuli twice a day for two weeks. The severity of tonic-clonic seizures and the severity of temporal lobe epilepsy seizures were evaluated by the mesencephalic severity index (Rossetti et al scale) and the limbic index (Racine's scale), respectively. Seizures were observed in both untreated (a high BP control) SHRs and in SHRs treated with AT1R antagonist and ACE inhibitor. There was no statistical difference in the mesencephalic severity and limbic index between these groups. Our results demonstrate, for the first time, that SHR present seizure susceptibility with acoustic stimulation. Moreover, although RAS inhibitors effectively reduce blood pressure in hypertensive rats, it does not prevent developing epileptic seizures upon audiogenic stimulation. In conclusion, our study shows that RAS is an unlikely link between hypertension and susceptibility to epileptic seizures in SHRs, which is in contrast with the anticonvulsant effect of losartan in animals of the genetically-epileptic Wistar Audiogenic Rat (WAR) strain.