AccScience Publishing / AN / Volume 2 / Issue 2 / DOI: 10.36922/an.0387
Submit to AN
Cite this article
58
Download
1376
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Effects of losartan and enalapril on lithium-pilocarpine-induced status epilepticus, spontaneous convulsive seizures, and cardiac changes in rats

Jatinder Katyal1* ,  Dinesh Joshi1 ,  Yogendra Kumar Gupta2
Show Less
1 Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
2 Translational Health Science and Technology Institute, Faridabad, Haryana, India
Advanced Neurology 2023, 2(2), 0387 https://doi.org/10.36922/an.0387
Submitted: 2 April 2023 | Accepted: 1 June 2023 | Published: 19 June 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Modulating the brain renin-angiotensin system presents an innovative pathway for exploring newer treatment approaches in epilepsy. The current study aimed to evaluate the influence of losartan (LOS) and enalapril (ENP), which are angiotensin receptor blocker and angiotensin-converting enzyme inhibitor, respectively, on the incidence, initiation, and duration of status epilepticus (SE), spontaneous convulsive seizures (SCS), survival, and cardiac alterations in rats subjected to lithium-pilocarpine (LiP)-induced SE. Lithium (127 mg/kg, i.p.) pretreated male Wistar rats were administered pilocarpine (30 mg/kg, i.p.) after 24 h to induce SE, which was terminated after 90 min of onset. Daily 10-h video monitoring was carried out for examining onset, frequency, duration of SCS, and mortality till 18 days. The administration of LOS (10 mg/kg, i.p.), ENP (20 mg/kg, i.p.) and atenolol (AT; 50 mg/kg, p.o.) was started before lithium in pre-SE protocol and for post-SE protocol these drugs were administered 1 h after terminating SE and continued for 7 days’ post-SE. Cardiac pathology, echocardiography, heart weight/body weight ratio, and histopathology were evaluated. None of the drugs used (LOS/ENP/AT) offered protection against SE. Administration before SE decreased and post-SE administration increased the latency of SCS, and the overall duration of seizures remained short in both cases as compared to untreated rats. The heart weight/body weight ratio decreased in rats that did not survive. No echocardiographic changes were observed in any of the groups. Untreated SE rats showed myocyte ischemic changes, which were not present in any treated rats. In conclusion, LOS may reduce cardiac complications in SE rats. Hence, further evaluation of LOS as an add-on in epilepsy treatment should be performed.

Keywords
Status epilepticus
Lithium-pilocarpine
Losartan
Enalapril
Atenolol
Spontaneous convulsive seizures
Cardiac changes
Funding
Research grant from the Department of Science and Technology, Science and Engineering Research Board, New Delhi, India
References
  1. Natelson BH, Suarez RV, Terrence CF, et al., 1998, Patients with epilepsy who die suddenly have cardiac disease. Arch Neurol, 55: 857–860. https://doi.org/10.1001/archneur.55.6.857

 

  1. Shimizu M, Kagawa A, Takano T, et al., 2008, Neurogenic stunned myocardium associated with status epileptics and postictal catecholamine surge. Intern Med, 47: 269–273. https://doi.org/10.2169/internalmedicine.47.0499

 

  1. Curia G, Longo D, Biagini G, et al., 2008, The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods, 172: 143–157. https://doi.org/10.1016/j.jneumeth.2008.04.019

 

  1. Damasceno DD, Ferreira AJ, Doretto MC, et al., 2012, Cardiovascular dysautonomia after seizures induced by maximal electroshock in Wistar rats. Seizure, 21: 711–716. https://doi.org/10.1016/j.seizure.2012.07.015

 

  1. Lotufo PA, Valiengo L, Benseñor IM, et al., 2012, A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs. Epilepsia, 53: 272–282. https://doi.org/10.1111/j.1528-1167.2011.03361.x

 

  1. Naggar I, Lazar J, Kamran H, et al., 2014, Relation of autonomic and cardiac abnormalities to ventricular fibrillation in a rat model of epilepsy. Epilepsy Res, 108: 44–56. https://doi.org/10.1016/j.eplepsyres.2013.10.018

 

  1. Argañaraz GA, Konno AC, Perosa SR, et al., 2008, The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis. Epilepsia, 49: 1348–1357. https://doi.org/10.1111/j.1528-1167.2008.01581.x

 

  1. Pereira MGAG, Becari C, Oliveira JAC, et al., 2010, Inhibition of the renin-angiotensin system prevents seizures in a rat model of epilepsy. Clin Sci (Lond), 119: 477–482. https://doi.org/10.1042/cs20100053

 

  1. Tchekalarova J, Georgiev V, 2005, Angiotensin peptides modulatory system: How is it implicated in the control of seizure susceptibility? Life Sci, 76: 955–970. https://doi.org/10.1016/j.lfs.2004.10.012

 

  1. Łukawski K, Jakubus T, Janowska A, et al., 2013, Enalapril enhances the anticonvulsant activity of lamotrigine in the test of maximal electroshock. Pharmacol Rep, 65: 1012–1017. https://doi.org/10.1016/s1734-1140(13)71083-1

 

  1. Joshi D, Katyal J, Arava S, et al., 2019, Effects of enalapril and losartan alone and in combination with sodium valproate on seizures, memory, and cardiac changes in rats. Epilepsy Behav, 92: 345–352. https://doi.org/10.1016/j.yebeh.2018.12.019

 

  1. Leite JP, Bortolotto ZA, Cavalheiro EA, 1990, Spontaneous recurrent seizures in rats: An experimental model of partial epilepsy. Neurosci Biobehav Rev, 14: 511–517. https://doi.org/10.1016/s0149-7634(05)80076-4

 

  1. Kumar H, Katyal J, Joshi D, et al., 2022, Effect of morphine administration after status epilepticus on epileptogenesis in rats. Epilepsy Behav, 135: 108905. https://doi.org/10.1016/j.yebeh.2022.108905

 

  1. Arida RM, Scorza FA, Peres CA, et al., 1999, The course of untreated seizures in the pilocarpine model of epilepsy. Epilepsy Res, 34: 99–107. https://doi.org/10.1016/s0920-1211(98)00092-8

 

  1. Goffin K, Nissinen J, Van Laere K, et al., 2007, Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in rat. Exp Neurol, 205: 501–505. https://doi.org/10.1016/j.expneurol.2007.03.008

 

  1. Okada S, Yokoyama M, Toko H, et al., 2012, Brain-derived neurotrophic factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-mediated pathway. Arterioscler Thromb Vasc Biol, 32: 1902–1909. https://doi.org/10.1161/atvbaha.112.248930

 

  1. Jaiswal A, Kumar S, Seth S, et al., 2010, Effect of U50,488H, a κ-opioid receptor agonist on myocardial α-and β-myosin heavy chain expression and oxidative stress associated with isoproterenol-induced cardiac hypertrophy in rat. Mol Cell Biochem, 345: 231–240. https://doi.org/10.1007/s11010-010-0577-4

 

  1. Lemos T, Cavalheiro EA, 1995, Suppression of pilocarpine-induced status epilepticus and the late development of epilepsy in rats. Exp Brain Res, 102: 423–428. https://doi.org/10.1007/bf00230647

 

  1. Klitgaard H, Matagne A, Vanneste-Goemaere J, et al., 2002, Pilocarpine-induced epileptogenesis in the rat: Impact of initial duration of status epilepticus on electrophysiological and neuropathological alterations. Epilepsy Res, 51: 93–107. https://doi.org/10.1016/s0920-1211(02)00099-2

 

  1. Löscher W, 2015, Single versus combinatorial therapies in status epilepticus: Novel data from preclinical models. Epilepsy Behav, 49: 20–25. https://doi.org/10.1016/j.yebeh.2015.02.027

 

  1. Baumann M, Janssen BJA, Hermans JJR, et al., 2007, Transient AT1 receptor-inhibition in prehypertensive spontaneously hypertensive rats results in maintained cardiac protection until advanced age. J Hypertens, 25: 207–215. https://doi.org/10.1097/HJH.0b013e3280102bff

 

  1. Ahmad M, 2013, Protective effects of curcumin against lithium-pilocarpine induced status epilepticus, cognitive dysfunction and oxidative stress in young rats. Saudi J Biol Sci, 20: 155–162. https://doi.org/10.1016/j.sjbs.2013.01.002

 

  1. Glien M, Brandt C, Potschka H, et al., 2001, Repeated low-dose treatment of rats with pilocarpine: Low mortality but high proportion of rats developing epilepsy. Epilepsy Res, 46: 111–119. https://doi.org/10.1016/s0920-1211(01)00272-8

 

  1. Noyan B, Güleç G, 2000, Effects of L-arginine on prevention and treatment of lithium-pilocarpine-induced status epilepticus. Physiol Res, 49: 379–385.

 

  1. Liu J, Wang A, Li L, et al., 2010, Oxidative stress mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus. Seizure, 19: 165–172. https://doi.org/10.1016/j.seizure.2010.01.010

 

  1. Tchekalarova JD, Ivanova NM, Pechlivanova DM, et al., 2014, Antiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy. Pharmacol Biochem Behav, 127: 27–36. https://doi.org/10.1016/j.pbb.2014.10.005

 

  1. Jope RS, Morrisett RA, Snead OC, 1986, Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats. Exp Neurol, 91: 471–480. https://doi.org/10.1016/0014-4886(86)90045-2

 

  1. Reno CM, Skinner A, Bayles J, et al., 2018, Severe hypoglycemia-induced sudden death is mediated by both cardiac arrhythmias and seizures. Am J Physiol Endocrinol Metab, 315: E240–E249. https://doi.org/10.1152/ajpendo.00442.2017

 

  1. Read MI, Harrison JC, Kerr DS, et al., 2015, Atenolol offers better protection than clonidine against cardiac injury in kainic acid-induced status epilepticus. Br J Pharmacol, 172: 4626–4638. https://doi.org/10.1111/bph.13132

 

  1. Read MI, Millen RN, McCann DM, et al., 2018, Improved cardiac outcomes with combined atenolol and diazepam intervention in seizure. Epilepsia, 59: 854–865. https://doi.org/10.1111/epi.14039

 

  1. Abiodun OA, Ola MS, 2020, Role of brain renin angiotensin system in neurodegeneration: An update. Saudi J Biol Sci, 27: 905–912. https://doi.org/10.1016/j.sjbs.2020.01.026

 

  1. Łukawski K, Czuczwar SJ, 2015, Effect of ACE inhibitors and AT1 receptor antagonists on pentylenetetrazole-induced convulsions in mice. Neurol Sci, 36: 779–781. https://doi.org/10.1007/s10072-014-2040-x

 

  1. De Sarro G, Di Paola ED, Gratteri S, et al., 2012, Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice. Pharmacol Res, 65: 285–296. https://doi.org/10.1016/j.phrs.2011.11.005

 

  1. Tchekalarova J, Loyens E, Smolders I, 2015, Effects of AT1 receptor antagonism on kainate-induced seizures and concomitant changes in hippocampal extracellular noradrenaline, serotonin, and dopamine levels in Wistar-Kyoto and spontaneously hypertensive rats. Epilepsy Behav, 46: 66–71. https://doi.org/10.1016/j.yebeh.2015.03.021

 

  1. Tchekalarova JD, Ivanova N, Atanasova D, et al., 2016, Long-term treatment with losartan attenuates seizure activity and neuronal damage without affecting behavioral changes in a model of co-morbid hypertension and epilepsy. Cell Mol Neurobiol, 36: 927–941. https://doi.org/10.1007/s10571-015-0278-3

 

  1. Sun H, Wu H, Yu X, et al., 2015, Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus. Mol Cell Neurosci, 65: 58–67. https://doi.org/10.1016/j.mcn.2015.02.014

 

  1. Gomes KP, Braga PPP, de Lima CQ, et al., 2020, Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy. Clin Sci (Lond), 134: 2263–2277. https://doi.org/10.1042/cs20200514

 

  1. Walton NY, Rubinstein BK, Treiman DM, 1995, Cardiac hypertrophy secondary to status epilepticus in the rat. Epilepsy Res, 20: 121–124. https://doi.org/10.1016/0920-1211(94)00074-7

 

  1. Painter JA, Shiel FO, DeLorenzo RJ, 1993, Cardiac pathology findings in status epilepticus. Epilepsia, 34: 30.

 

  1. Melenovsky V, Skaroupkova P, Benes J, et al., 2012, The course of heart failure development and mortality in rats with volume overload due to aorto-caval fistula. Kidney Blood Press Res, 35: 167–173. https://doi.org/10.1159/000331562

 

  1. Turski L, Ikonomidou C, Turski WA, et al., 1989, Review: Cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: A novel experimental model of intractable epilepsy. Synapse, 3: 154–171. https://doi.org/10.1002/syn.890030207

 

  1. Ben-Menachem E, 2007, Weight issues for people with epilepsy--a review. Epilepsia, 48: 42–45. https://doi.org/10.1111/j.1528-1167.2007.01402.x

 

  1. Cabassi A, Coghi P, Govoni P, et al., 2005, Sympathetic modulation by carvedilol and losartan reduces angiotensin II-mediated lipolysis in subcutaneous and visceral fat. J Clin Endocrinol Metab, 90: 2888–2897. https://doi.org/10.1210/jc.2004-1995

 

  1. Bailey CJ, Thornburn CC, Flatt PR, 1986, Effects of ephedrine and atenolol on the development of obesity and diabetes in ob/ob mice. Gen Pharmacol, 17: 243–246. https://doi.org/10.1016/0306-3623(86)90147-3
Conflict of interest
The authors have no conflict of interest.
Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept