Generic placeholder image

Current Hypertension Reviews

Editor-in-Chief

ISSN (Print): 1573-4021
ISSN (Online): 1875-6506

Research Article

Montelukast Ameliorates 2K1C-Hypertension Induced Endothelial Dysfunction and Associated Vascular Dementia

Author(s): Surbhi Gupta, Prabhat Singh* and Bhupesh Sharma

Volume 20, Issue 1, 2024

Published on: 08 January, 2024

Page: [23 - 35] Pages: 13

DOI: 10.2174/0115734021276985231204092425

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are serious public health concerns, which highlights the urgent need for study on the risk factors for cognitive decline. Cysteinyl leukotriene (CysLT1) receptors are concerned with regulating cognition, motivation, inflammatory processes, and neurogenesis.

Objective: This research aims to examine the consequence of montelukast (specific CysLT1 antagonist) in renovascular hypertension 2-kidney-1-clip-2K1C model-triggered VaD in experimental animals.

Methods: 2K1C tactics were made to prompt renovascular hypertension in mature male rats. Morris water maze was employed to measure cognition. Mean arterial pressure (MAP), serum nitrite levels, aortic superoxide content, vascular endothelial activity, brain’s oxidative stress (diminished glutathione, raised lipid peroxides), inflammatory markers (IL-10, IL-6, TNF-α), cholinergic activity (raised acetylcholinesterase), and cerebral injury (staining of 2, 3, 5- triphenylterazolium chloride) were also examined.

Results: Montelukast in doses of 5.0 and 10.0 mg kg-1 was used intraperitoneally as the treatment drug. Along with cognitive deficits, 2K1C-operated rats showed elevated MAP, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage with diminished serum nitrite/nitrate. Montelukast therapy significantly and dose-dependently mitigated the 2K1Chypertension- provoked impaired behaviors, biochemistry, endothelial functions, and cerebral infarction.

Conclusion: The 2K1C tactic caused renovascular hypertension and associated VaD, which was mitigated via targeted regulation of CysLT1 receptors by montelukast administration. Therefore, montelukast may be taken into consideration for the evaluation of its complete potential in renovascular-hypertension-induced VaD.

Keywords: Endothelium, hypertension, dementia, inflammation, montelukast, oxidative injury.

Graphical Abstract
[1]
Sharma P, Gaur N, Jayant S, et al. Salubrious effects of ulinastatin and quercetin alone or in combination in endothelial dysfunction and vascular dementia. Pharmacol Rep 2022; 74(3): 481-92.
[http://dx.doi.org/10.1007/s43440-022-00364-1] [PMID: 35396697]
[2]
Singh P, Sharma B. Selective serotonin-norepinephrine re-uptake inhibition limits renovas-cular-hypertension induced cognitive impairment, endothelial dysfunction, and oxidative stress injury. Curr Neurovasc Res 2016; 13(2): 135-46. [a]
[http://dx.doi.org/10.2174/1567202613666160226152549 ] [PMID: 26915517 ]
[3]
Sharma B, Singh N. Salutary effect of NFκB inhibitor and folacin in hyperhomocysteinemia–hyperlipidemia induced vascular dementia. Prog Neuropsychopharmacol Biol Psychiatry 2012; 38(2): 207-15.
[http://dx.doi.org/10.1016/j.pnpbp.2012.03.013] [PMID: 22510463]
[4]
Sharma P, Kaushik P, Jain S, et al. Efficacy of ulinastatin and sulforaphane alone or in combination in rat model of streptozotocin diabetes induced vascular dementia. Clin Psychopharmacol Neurosci 2021; 19(3): 470-89.
[http://dx.doi.org/10.9758/cpn.2021.19.3.470] [PMID: 34294616]
[5]
Pires PW, Girgla SS, McClain JL, Kaminski NE, van Rooijen N, Dorrance AM. Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion. Microcirculation 2013; 20(7): 650-61.
[http://dx.doi.org/10.1111/micc.12064] [PMID: 23647512]
[6]
Santisteban MM, Iadecola C, Carnevale D. Hypertension, neurovascular dysfunction, and cognitive impairment. Hypertension 2023; 80(1): 22-34.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.122.18085] [PMID: 36129176]
[7]
Chen J, Li CG, Yang LX, et al. MYPT1SMKO Mice Function as a Novel Spontaneous Age- and Hypertension-Dependent Animal Model of CSVD. Transl Stroke Res 2023. Online ahead of print
[http://dx.doi.org/10.1007/s12975-023-01142-8] [PMID: 36843141]
[8]
Zhang XY, Wang XR, Xu DM, et al. HAMI 3379, a CysLT2 receptor antagonist, attenuates ischemia-like neuronal injury by inhibiting microglial activation. J Pharmacol Exp Ther 2013; 346(2): 328-41.
[http://dx.doi.org/10.1124/jpet.113.203604] [PMID: 23750020]
[9]
Attaluri S, Upadhya R, Kodali M, et al. Brain-specific increase in leukotriene signaling accompanies chronic neuroinflammation and cognitive impairment in a model of Gulf war illness. Front Immunol 2022; 13: 853000.
[http://dx.doi.org/10.3389/fimmu.2022.853000] [PMID: 35572589]
[10]
Michael J, Marschallinger J, Aigner L. The leukotriene signaling pathway: a druggable target in Alzheimer’s disease. Drug Discov Today 2019; 24(2): 505-16.
[http://dx.doi.org/10.1016/j.drudis.2018.09.008] [PMID: 30240876]
[11]
Xiong LY, Ouk M, Wu CY, et al. Leukotriene receptor antagonist use and cognitive decline in normal cognition, mild cognitive impairment, and Alzheimer’s dementia. Alzheimers Res Ther 2021; 13(1): 147.
[http://dx.doi.org/10.1186/s13195-021-00892-7] [PMID: 34479635]
[12]
Tassan Mazzocco M, Murtaj V, Martins D, et al. Exploring the neuroprotective effects of montelukast on brain inflammation and metabolism in a rat model of quinolinic acid-induced striatal neurotoxicity. J Neuroinflammation 2023; 20(1): 34.
[http://dx.doi.org/10.1186/s12974-023-02714-z] [PMID: 36782185]
[13]
Zhou L, Sun X, Shi Y, Liu J, Luan G, Yang Y. Cysteinyl leukotriene receptor type 1 antagonist montelukast protects against injury of blood–brain barrier. Inflammopharmacology 2019; 27(5): 933-40.
[http://dx.doi.org/10.1007/s10787-019-00611-7] [PMID: 31313075]
[14]
Eriksson Y, Boström M, Sandelius Å, et al. The anti-asthmatic drug, montelukast, modifies the neurogenic potential in the young healthy and irradiated brain. Cell Death Dis 2018; 9(7): 775.
[http://dx.doi.org/10.1038/s41419-018-0783-7] [PMID: 29991719]
[15]
Bıber N, Toklu HZ, Solakoglu S, et al. Cysteinyl-leukotriene receptor antagonist montelukast decreases blood–brain barrier permeability but does not prevent oedema formation in traumatic brain injury. Brain Inj 2009; 23(6): 577-84.
[http://dx.doi.org/10.1080/02699050902926317 ] [PMID: 19484631 ]
[16]
Yu GL, Wei EQ, Zhang SH, et al. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time-dependently protects against focal cerebral ischemia in mice. Pharmacology 2005; 73(1): 31-40.
[http://dx.doi.org/10.1159/000081072] [PMID: 15452361]
[17]
Datusalia AK, Singh G, Yadav N, Gaun S, Manik M, Singh RK. Targeted delivery of montelukast for the treatment of alzheimer’s disease. CNS Neurol Disord Drug Targets 2022; 21(10): 913-25.
[http://dx.doi.org/10.2174/1871527320666210902163756]
[18]
Wallin J, Svenningsson P. Potential Effects of Leukotriene Receptor Antagonist Montelukast in Treatment of Neuroinflammation in Parkinson’s Disease. Int J Mol Sci 2021; 22(11): 5606.
[http://dx.doi.org/10.3390/ijms22115606] [PMID: 34070609]
[19]
Kapelka I, Shtrygol S, Koiro O, Merzlikin S, Kudina O, Yudkevych T. Effect of arachidonic acid cascade inhibitors on body temperature and cognitive functions in rats in the Morris water maze after acute cold injury. Pharmazie 2021; 76(7): 313-6.
[PMID: 34256893]
[20]
Singh P, Sharma B. Reversal in cognition impairments, cholinergic dysfunction, and cerebral oxidative stress through the modulation of ryanodine receptors (RyRs) and cysteinyl leukotriene-1 (CysLT1) receptors. Curr Neurovasc Res 2016; 13(1): 10-21.
[http://dx.doi.org/10.2174/1567202612666151026105610] [PMID: 26500103]
[21]
Singh P, Gupta S, Sharma B. Antagonism of endothelin (ETA and ETB) receptors during renovascular hypertension-induced vascular dementia improves cognition. Curr Neurovasc Res 2016; 13(3): 219-29.
[http://dx.doi.org/10.2174/1567202613666160518122534] [PMID: 27189349]
[22]
Gupta S, Sharma B. Protective effects of phosphodiesterase-1 (PDE1) and ATP sensitive potassium (KATP) channel modulators against 3-nitropropionic acid induced behavioral and biochemical toxicities in experimental Huntington׳s disease. Eur J Pharmacol 2014; 732: 111-22.
[http://dx.doi.org/10.1016/j.ejphar.2014.03.032] [PMID: 24690258]
[23]
Singh P, Sharma B. Agonism of Histaminergic-H1 Receptors in Ischemic Postconditioning During Cerebral Ischemia-Reperfusion Injury is Protective. Curr Neurovasc Res 2021; 17(5): 686-99.
[http://dx.doi.org/10.2174/1567202617666201214105720] [PMID: 33319685]
[24]
Beutler RG. Reduced glutathion estimation. J Lab Clin Med 1963; 61: 82.
[25]
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-8.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[26]
Ellman GL, Courtney KD, Andres V Jr, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961; 7(2): 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[27]
Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[28]
Iampanichakul M, Poasakate A, Potue P, et al. Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats. Sci Rep 2022; 12(1): 9289.
[http://dx.doi.org/10.1038/s41598-022-13513-6] [PMID: 35662276]
[29]
Botros FT, Schwartzman ML, Stier CT Jr, Goodman AI, Abraham NG. Increase in heme oxygenase-1 levels ameliorates renovascular hypertension. Kidney Int 2005; 68(6): 2745-55.
[http://dx.doi.org/10.1111/j.1523-1755.2005.00745.x] [PMID: 16316349]
[30]
Faraco G, Iadecola C. Hypertension: a harbinger of stroke and dementia. Hypertension 2013; 62(5): 810-7.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01063] [PMID: 23980072]
[31]
Chan SL, Baumbach GL. Nox2 deficiency prevents hypertension-induced vascular dysfunction and hypertrophy in cerebral arterioles. Int J Hypertens 2013; 2013: 793630.
[http://dx.doi.org/10.1155/2013/793630]
[32]
Rojas-Franco P, Garcia-Pliego E, Vite-Aquino AG, et al. The nutraceutical antihypertensive action of C-phycocyanin in chronic kidney disease is related to the prevention of endothelial dysfunction. Nutrients 2022; 14(7): 1464.
[http://dx.doi.org/10.3390/nu14071464] [PMID: 35406077]
[33]
Gao Y, Li W, Liu Y, et al. Effect of telmisartan on preventing learning and memory deficits via peroxisome proliferator-activated receptor-γ in vascular dementia spontaneously hypertensive rats. J Stroke Cerebrovasc Dis 2018; 27(2): 277-85.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2017.01.025] [PMID: 29241675]
[34]
Carvalho C, Moreira PI. Oxidative stress: a major player in cerebrovascular alterations associated to neurodegenerative events. Front Physiol 2018; 9: 806.
[http://dx.doi.org/10.3389/fphys.2018.00806] [PMID: 30018565]
[35]
Bao C, He Q, Wang H, et al. Artemisinin and Its Derivate Alleviate Pulmonary Hypertension and Vasoconstriction in Rodent Models. Oxid Med Cell Longev 2022; 2022: 1-21.
[http://dx.doi.org/10.1155/2022/2782429] [PMID: 35757500]
[36]
Virdis A, Duranti E, Taddei S. Oxidative stress and vascular damage in hypertension: Role of angiotensin II. Int J Hypertens 2011; 2011: 916310.
[http://dx.doi.org/10.4061/2011/916310]
[37]
Ali M, Singh P, Singh L, Pandey RK, Soni P, Singh A. Neuroprotective Effect of Morinda citrifolia on Behavioural and Biochemical Deficits in PTZ-induced Kindled Mice. Infect Disord Drug Targets 2023; 23(8): e050623217670.
[http://dx.doi.org/10.2174/1871526523666230605160222] [PMID: 37282657]
[38]
Beswick RA, Dorrance AM, Leite R, Webb RC. NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. Hypertension 2001; 38(5): 1107-11.
[http://dx.doi.org/10.1161/hy1101.093423] [PMID: 11711506]
[39]
Brennan LA, Kantorow M. Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations. Exp Eye Res 2009; 88(2): 195-203.
[http://dx.doi.org/10.1016/j.exer.2008.05.018] [PMID: 18588875]
[40]
Lefebvre B, Caron F, Bessard G, Stanke-Labesque F. Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats. J Hypertens 2006; 24(1): 85-93.
[http://dx.doi.org/10.1097/01.hjh.0000198027.76729.b8] [PMID: 16331105]
[41]
Schwimmbeck F, Staffen W, Höhn C, et al. Cognitive effects of montelukast: a pharmaco-EEG study. Brain Sci 2021; 11(5): 547.
[http://dx.doi.org/10.3390/brainsci11050547] [PMID: 33925326]
[42]
Kumar A, Prakash A, Pahwa D, Mishra J. Montelukast potentiates the protective effect of rofecoxib against kainic acid-induced cognitive dysfunction in rats. Pharmacol Biochem Behav 2012; 103(1): 43-52.
[http://dx.doi.org/10.1016/j.pbb.2012.07.015] [PMID: 22878042]
[43]
Lai J, Hu M, Wang H, et al. Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice. Neuropharmacology 2014; 79: 707-14.
[http://dx.doi.org/10.1016/j.neuropharm.2014.01.011] [PMID: 24456746]
[44]
Fei Z, Zhang L, Wang L, Jiang H, Peng A. Montelukast ameliorated pemetrexed-induced cytotoxicity in hepatocytes by mitigating endoplasmic reticulum (ER) stress and nucleotide oligomerization domain-like receptor protein 3 (NLRP3) activation. Bioengineered 2022; 13(3): 7894-903.
[http://dx.doi.org/10.1080/21655979.2022.2051689] [PMID: 35291928]
[45]
Mazzetti L, Franchi-Micheli S, Nistri S, et al. The ACh-induced contraction in rat aortas is mediated by the Cys Lt1 receptor via intracellular calcium mobilization in smooth muscle cells. Br J Pharmacol 2003; 138(4): 707-15.
[http://dx.doi.org/10.1038/sj.bjp.0705087] [PMID: 12598425]
[46]
Rundell KW, Steigerwald MD, Fisk MZ. Montelukast prevents vascular endothelial dysfunction from internal combustion exhaust inhalation during exercise. Inhal Toxicol 2010; 22(9): 754-9.
[http://dx.doi.org/10.3109/08958371003743254] [PMID: 20462392]
[47]
Abdelzaher LA, Hussein OA, Ashry IEM. The novel potential therapeutic utility of montelukast in alleviating autistic behavior induced by early postnatal administration of thimerosal in mice. Cell Mol Neurobiol 2021; 41(1): 129-50.
[http://dx.doi.org/10.1007/s10571-020-00841-2] [PMID: 32303879]
[48]
Huang XQ, Zhang XY, Wang XR, et al. Transforming growth factor β1-induced astrocyte migration is mediated in part by activating 5-lipoxygenase and cysteinyl leukotriene receptor 1. J Neuroinflammation 2012; 9(1): 145.
[http://dx.doi.org/10.1186/1742-2094-9-145] [PMID: 22734808]
[49]
Stein DG, Hoffman SW. Estrogen and progesterone as neuroprotective agents in the treatment of acute brain injuries. Pediatr Rehabil 2003; 6(1): 13-22.
[http://dx.doi.org/10.1080/1363849031000095279] [PMID: 12745891]
[50]
Datto JP, Bastidas JC, Miller NL, et al. Female rats demonstrate improved locomotor recovery and greater preservation of white and gray matter after traumatic spinal cord injury compared to males. J Neurotrauma 2015; 32(15): 1146-57.
[http://dx.doi.org/10.1089/neu.2014.3702] [PMID: 25715192]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy