Ameliorative Effect of a Selective Endothelin ETA Receptor Antagonist in Rat Model of L-Methionine-induced Vascular Dementia
The Korean Journal of Physiology and Pharmacology
; : 201-209, 2014.
Article
in En
| WPRIM
| ID: wpr-727675
Responsible library:
WPRO
ABSTRACT
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Acetylcholinesterase
/
Brain
/
Dementia, Vascular
/
Endothelins
/
Thiobarbituric Acid Reactive Substances
/
Hyperhomocysteinemia
/
Models, Animal
/
Glutathione
/
Learning
/
Memory
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2014
Type:
Article