Korean J Physiol Pharmacol.  2014 Jun;18(3):201-209. 10.4196/kjpp.2014.18.3.201.

Ameliorative Effect of a Selective Endothelin ETA Receptor Antagonist in Rat Model of L-Methionine-induced Vascular Dementia

  • 1Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala (Punjab) 147002, India. nirmal_puru@rediffmail.com


The present study was designed to investigate the efficacy of selective ET(A) receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from 5th to 8th week of L-methionine treatment). On 52nd day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective ET(A) receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.


Ambrisen; L-Methionine; Morris water-maze; Vascular dementia
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