Losartan suppresses the kainate-induced changes of angiotensin AT(1) receptor 
expression in a model of comorbid hypertension and epilepsy.

Atanasova, D. Y.; Tchekalarova, J.; Ivanova, N.; Nenchovska, Z.; Pavlova, E.; Atanassova, N.; Lazarov, N.

doi:10.1016/j.lfs.2017.12.006

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Losartan suppresses the kainate-induced changes of angiotensin AT(1) receptor expression in a model of comorbid hypertension and epilepsy.

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Atanasova, D. Y.
Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Atanasova, D. Y., Tchekalarova, J., Ivanova, N., Nenchovska, Z., Pavlova, E., Atanassova, N., et al. (2018). Losartan suppresses the kainate-induced changes of angiotensin AT(1) receptor expression in a model of comorbid hypertension and epilepsy. Life Sciences, 193, 40-46. doi:10.1016/j.lfs.2017.12.006.

Cite as: https://hdl.handle.net/21.11116/0000-0000-269F-3

Abstract

Aims: Experimental and clinical studies have demonstrated that components of renin-angiotensin system are elevated in the hippocampus in epileptogenic conditions. In the present work, we explored the changes in the expression of angiotensin II receptor, type 1 (AT(1) receptor) in limbic structures, as well as the effect of the AT(1) receptor antagonist losartan in a model of comorbid hypertension and epilepsy. Main methods: The expression of AT(1) receptors was compared between spontaneously hypertensive rats (SHRs) and Wistar rats by using immunohistochemistry in the kainate (KA) model of temporal lobe epilepsy (TLE). The effect of losartan was studied on AT(1) receptor expression in epileptic rats that were treated for a period of 4 weeks after status epilepticus. Key findings: The naive and epileptic SHRs were characterized by stronger protein expression of AT(1) receptor than normotensive Wistar rats in the CA1, CA3a, CA3b, CA3c field and the hilus of the dentate gyrus of the dorsal hippocampus but fewer cells were immunostained in the piriform cortex. Increased AT(1) immunostaining was observed in the basolateral amygdala of epileptic SHRs but not of epileptic Wistar rats. Losartan exerted stronger and structure-dependent suppression of AT(1) receptor expression in SHRs compared to Wistar rats. Significance: Our results confirm the important role of AT(1) receptor in epilepsy and suggest that the AT(1) receptor antagonists could be used as a therapeutic strategy for treatment of comorbid hypertension and epilepsy.