Cardiovascular changes in genetic absence epileptic WAG/Rij rats: Effects of chronic ethosuximide treatment
Öz
Purpose: The aim of this study was to investigate the effects of chronic ethosuximide (ETX) treatment on absence seizures and cardiovascular parameters in WAG/Rij rats with genetic absence epilepsy.
Materials and Methods: Eight-weeks old, male Wistar and WAG/Rij rats were divided into four groups (n=20): Wistar control, Wistar ETX, WAG/Rij control and WAG/Rij ETX. ETX groups received chronic ETX treatment (oral, 300 mg/kg/day) for 3 months. At the end of the 3-month-treatment period; the total and mean duration, also number of spike wave discharges (SWDs) were evaluated using EEG recordings. Mean arterial blood pressure (MAP) and heart rate (HR) measurements were performed.
Results: ETX treatment significantly decreased the duration and frequency of SWDs in WAG/Rij rats. MAP in WAG/Rij control group was markedly higher than Wistar control group. In Wistar ETX group, HR was significantly slower than Wistar control group. KCl-induced contraction response enhanced in Wistar ETX group and diminished in WAG/Rij control group compared to Wistar control group.
Conclusion: Increased MAP and vascular reactivity in WAG/Rij rats. ETX treatment did not alter cardiovascular parameters in WAG/Rij rats whereas the treatment decreased the HR and vascular reactivity without affecting MAP in Wistar rats. T-type Ca++ channels may play a role in these changes.
Materials and Methods: Eight-weeks old, male Wistar and WAG/Rij rats were divided into four groups (n=20): Wistar control, Wistar ETX, WAG/Rij control and WAG/Rij ETX. ETX groups received chronic ETX treatment (oral, 300 mg/kg/day) for 3 months. At the end of the 3-month-treatment period; the total and mean duration, also number of spike wave discharges (SWDs) were evaluated using EEG recordings. Mean arterial blood pressure (MAP) and heart rate (HR) measurements were performed.
Results: ETX treatment significantly decreased the duration and frequency of SWDs in WAG/Rij rats. MAP in WAG/Rij control group was markedly higher than Wistar control group. In Wistar ETX group, HR was significantly slower than Wistar control group. KCl-induced contraction response enhanced in Wistar ETX group and diminished in WAG/Rij control group compared to Wistar control group.
Conclusion: Increased MAP and vascular reactivity in WAG/Rij rats. ETX treatment did not alter cardiovascular parameters in WAG/Rij rats whereas the treatment decreased the HR and vascular reactivity without affecting MAP in Wistar rats. T-type Ca++ channels may play a role in these changes.
Anahtar Kelimeler
Absence epilepsy, WAG/Rij, ethosuximide, heart rate, blood pressure, vascular reactivity
Proje Numarası
SBAG / 114S481
Kaynakça
- Jansen K, Lagae L. Cardiac changes in epilepsy. Seizure. 2010;19(8):455-60.
- Velagapudi P, Turagam M, Laurence T, Kocheril A. Cardiac arrhythmias and sudden unexpected death in epilepsy (SUDEP). Pacing Clin Electrophysiol. 2012;35(3):363-70.
- Depaulis A, Charpier S. Pathophysiology of absence epilepsy: Insights from genetic models. Neurosci Lett. 2018;667:53-65.
- Depaulis A, van Luijtelaar G. Genetic models of absence epilepsy in the rat. In Models of Seizures and Epilepsy (Eds A Pitkänen, PA Schwartkroin, SL Moshe):233-248. Amsterdam, Elsevier, 2006.
- Karson AB, Aker R, Ateş N, Onat F. Cardiovascular effects of intracerebroventricular bicuculline in rats with absence seizures. Epilepsy Res. 1999;34(2-3):231-9.
- Aker RG, Onat FY. Cardiovascular regulation through hypothalamic GABA(A) receptors in a genetic absence epilepsy model in rat. Epilepsia. 2002;43(2):107-14.
- Yananli HR, Terzioğlu B, Goren MZ, Aker RG, Aypak C, Onat FY. Extracellular hypothalamic gamma-aminobutyric acid (GABA) and L-glutamic acid concentrations in response to bicuculline in a genetic absence epilepsy rat model. J Pharmacol Sci. 2008;106(2):301-9.
- Powell KL, Jones NC, Kennard JT, Ng C, Urmaliya V, Lau S et al. HCN channelopathy and cardiac electrophysiologic dysfunction in genetic and acquired rat epilepsy models. Epilepsia. 2014;55(4):609-20.
- Cheong E, Shin HS. T-type Ca++ channels in absence epilepsy. Biochim Biophys Acta. 2013;1828(7):1560-71.
- Kessler SK, McGinnis E. A Practical Guide to Treatment of Childhood Absence Epilepsy. Paediatr Drugs. 2019;21(1):15-24.
