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

Abstract

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