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.