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Effects of antihypertensive agents on Alzheimer’s disease biomarkers in hypertensive rats with experimentally induced Alzheimer’s

Marwan Qasim Nadir
Department of Pharmacology, Medical Physics, and Biochemistry, College of Medicine, Hawler Medical University, Erbil, Iraq.
Rojgar Hamed Ali
Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
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Copyright (c) 2026 Marwan Qasim Nadir, Rojgar Hamed Ali (Author)

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Abstract

Background and objective: The most common cause of dementia in the elderly is Alzheimer's disease (AD). Numerous research studies have demonstrated a connection between hypertension (HTN) and the risk of developing AD. An increasing amount of evidence indicates that cognitive function significantly declines in HTN patients due to pathogenic pathways such as atherosclerosis, arteriolosclerosis, stroke, and cerebral ischemia. This study aims to investigate the effects of antihypertensive drugs on AD onset and levels of AD biomarkers in a rat model of HTN–AD. Oral N-nitro-L-arginine methyl ester hydrochloride (L-NAME HCl) and intraperitoneal injections of scopolamine were used to induce HTN and AD, respectively.

Methods: Forty-two female Wistar albino rats were split into seven groups of six rats. Group I represented the negative control group. The six experimental groups received scopolamine (2 mg/kg) and L-NAME HCl (40 mg/kg), administered intraperitoneally. Group II represented the positive control. The rats in Groups III, IV, V, VI, and VII received a daily oral dose of donepezil (10mg/kg), telmisartan (10mg/kg), amlodipine (5mg/kg), bisoprolol (10mg/kg), or bumetanide (20mg/kg), respectively. Differences for all parameters were assessed using one-way analysis of variance, including for BP, between the control and drug-treated rats using the Statistical Package for Social Science (version 27). Statistical significance was assessed using the P-value<0.05

Results: Inducing HTN and AD in rats significantly elevated the levels of all serum parameters compared to the control group, alongside a noticeable rise in brain parameters. The largest statistically significant decreases—in serum tumor necrosis factor alpha, interleukin-6, and C-reactive protein—were noted in telmisartan-treated rats. The most statistically significant decrease in brain acetylcholinesterase was seen in bumetanide-treated rats. On the other hand, donepezil-treated rats showed the largest statistically significant decreases in brain amyloid-β 42, β-secretase, phosphorylated microtubule-associated protein tau, malondialdehyde, nitric oxide, serum total tau protein, and serum amyloid-β 42. Bumetanide-treated rats showed the greatest performance on the spontaneous alternation (73.66%) and total arm entry tests (57.66) compared those in the other treatment groups, while donepezil-treated rats spent more time (5.42 minutes) in the novel arms compared to those of the other groups.

Conclusion: All the antihypertensive medications examined in this investigation effectively reduced the majority of plasma and brain biomarkers and therefore show great therapeutic potential, particularly bumetanide and telmisartan. According to this study, telmisartan and bumetanide, either alone or in combination with donepezil, may be effective medication options for neurodegeneration and risk mitigation in AD patients who also have HTN.

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How to Cite
Qasim Nadir, M., & Hamed Ali, R. (2026). Effects of antihypertensive agents on Alzheimer’s disease biomarkers in hypertensive rats with experimentally induced Alzheimer’s. Zanco Journal of Medical Sciences (ZJMS), 30(1), 246–270. https://doi.org/10.15218/zjms.2026.018

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