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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Montelukast Ameliorates 2K1C-Hypertension Induced Endothelial Dysfunction and Associated Vascular Dementia
Surbhi Gupta1, Prabhat Singh2, Bhupesh Sharma3
1Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India.
Insights
Hypertension-induced vascular dementia in rats was reversed by montelukast, a CysLT1 antagonist. This drug reduced cognitive deficits, oxidative stress, and inflammation, offering potential for treating renovascular hypertension-related brain injury.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Pharmacology
Background:
- Declined kidney function and hypertension are linked to cognitive deficits, dementia, and brain injury.
- Vascular dementia (VaD) poses a significant public health challenge, necessitating research into its risk factors.
- Cysteinyl leukotriene (CysLT1) receptors play a role in cognition, inflammation, and neurogenesis.
Purpose of the Study:
- To investigate the effects of montelukast, a CysLT1 antagonist, on vascular dementia (VaD) induced by renovascular hypertension in a 2-kidney-1-clip (2K1C) rat model.
- To assess montelukast's potential to mitigate cognitive decline and associated pathological changes.
Main Methods:
- Renovascular hypertension was induced in male rats using the 2K1C model.
- Cognitive function was evaluated using the Morris water maze.
- Measurements included mean arterial pressure, oxidative stress markers, inflammatory cytokines, endothelial function, and cerebral injury.
Main Results:
- 2K1C rats exhibited cognitive deficits, elevated blood pressure, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage.
- Montelukast treatment (5.0 and 10.0 mg kg-1) dose-dependently improved cognitive behavior and reduced biochemical and pathological markers.
- Therapy with montelukast mitigated hypertension-induced impairments in behavior, biochemistry, endothelial function, and cerebral infarction.
Conclusions:
- The 2K1C model successfully induced renovascular hypertension and associated vascular dementia (VaD).
- Montelukast administration effectively mitigated the effects of renovascular hypertension-induced VaD by targeting CysLT1 receptors.
- Montelukast shows promise for further evaluation in treating renovascular hypertension-induced VaD.
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.
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