AT1 receptor blocker candesartan-induced attenuation of brain injury of rats subjected to chronic cerebral hypoperfusion.
One of common pathophysiological states associated with central nervous system is chronic cerebral hypoperfusion (CH) that frequently occurs in conditions such as vascular dementia and Alzheimer's disease. Long term blockage of angiotensin II type 1 (AT(1)) receptor provides protection from ischemia induced injury of brain as well as reduction of cerebrovascular inflammation. Examining effect of the blockage on reduced glutathione (GSH), ascorbic acid (AA), and lipid peroxidation were of purpose in the present study. Modeling CH, rats were subjected to permanent occlusion of common carotid arteries bilaterally. AT(1 )receptor antagonist, candesartan, was given daily for 14 days after surgery. CH caused a significant increase in lipid peroxidation and decrease in GSH content of cerebral hippocampal tissue with no change in AA level. Candesartan (0.5 mg/kg, oral) not only reduced lipid peroxidation but also restored GSH significantly besides elevating AA and improving histopathological alterations. In conclusion, long term AT(1 )receptor blockage may be considered as novel therapeutic approach for protection from damage associated with CH. Underlying mechanism(s) may in part be related to suppressing oxidative stress and preserving brain antioxidant capacity.
Ozacmak
Veysel Haktan
VH
Department of Physiology, School of Medicine, Zonguldak Karaelmas University, Kozlu, Zonguldak, Turkey. vhaktan@yahoo.com
Sayan
Hale
H
Cetin
Alpay
A
Akyildiz-Igdem
Aysenur
A
D047228:Angiotensin II Type 1 Receptor Blockers / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001562:Benzimidazoles / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy*; D002545:Brain Ischemia; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D008297:Male; D016877:Oxidants / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C081643:candesartan