Antagonism of Endothelin (ETA and ETB) Receptors During Renovascular Hypertension-Induced Vascular Dementia Improves Cognition

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

Journal Name: Current Neurovascular Research

Volume 13 , Issue 3 , 2016

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Abstract:

Background: Diseases of cardio, as well as the cerebrovascular system, are known as the primary possibility for deficits in cognitive processes and dementia of vascular nature. Endothelin-1 (ET-1) and its receptors are extensively expressed in brain.

Objective: The present study has been structured to explore the effects of bosentan, an ET-1 antagonist on two-kidneyone- clip: 2K1C method induced hypertension provoked vascular dementia (VaD).

Method: 2K1C was modelled to induce renovascular hypertension. Mean arterial blood pressure (MABP) was assessed using BIOPAC system. Cognitive impairment was assessed employing Elevated plus maze-EPM as well as Morris water maze-MWM. Brain cholinergic dysfunction (activity of acetylcholinesterase-AChE), oxidative stress (thiobarbituric acid reactive substances-TBARS level, glutathione-GSH content, superoxide dismutase-SOD as well as catalase-CAT activity), aortic oxidative stress (superoxide anion level), serum nitrosative stress (nitrite/nitrate level), brain inflammation (myeloperoxidase-MPO), vascular endothelial dysfunction (endothelium-dependent relaxation) and infarct size (2,3,5- triphenyltetrazolium chloride-TTC staining) were assessed.

Results: Renal artery ligated animals have shown elevated oxidative stress in the aorta (superoxide anion-SA) and brain (augmented TBARS, with decreased GSH, SOD, and CAT). Similarly, 2K1C-renovascular hypertension has shown a considerable rise in brain inflammation (MPO activity) and brain AChE activity with a significant fall in serum nitrite/ nitrate contents. Administration of bosentan considerably diminished 2K1C hypertension induced alterations in MABP, cognitive impairment, and dysfunction of endothelium. Treatment with bosentan has also restored 2K1C induced a rise in brain TBARS, AChE, MPO activity, reduction in brain GSH, SOD and CAT as well as brain damage.

Conclusion: It may be concluded that ET-1 antagonism may be regarded as possible agents for managing renovascular hypertension induced VaD.

Keywords: Acetylcholinesterase, bosentan, 2, 3, 5-triphenylterazolium chloride staining, myeloperoxidase.

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Article Details

VOLUME: 13
ISSUE: 3
Year: 2016
Page: [219 - 229]
Pages: 11
DOI: 10.2174/1567202613666160518122534
Price: $58

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