Angiotensin receptor gene expression in candesartan mediated neuroprotection.
Male Wistar rats were treated with an angiotensin AT1 receptor antagonist, candesartan cilexetil (TCV-116, 1 mg/kg/day) over a 4-week period. Systolic blood pressure was significantly reduced by 14% after 1 week and remained stable for the next 3 weeks compared with controls. Up-regulation of AT2, but not AT1, receptor gene expression by 3.4-fold and 5.0-fold was observed 1 and 4 weeks after treatment. Middle cerebral artery occlusion caused significantly reduced infarct volumes in TCV-116-treated rats, by about 30% when compared with control rats. Neurological scores were also improved in treated rats. These results suggest that the neuroprotective effects of TCV-116 may be mediated through AT1 receptor antagonism and AT2 receptor up-regulation.
Lu
Qing
Q
Department of Pharmacology, Faculty of Medicine, National University of Singapore, 18 Medical Drive, Singapore 117597.
Zhu
Yi-Zhun
YZ
Wong
Peter T-H
PT
D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D007839:Functional Laterality / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy; D008297:Male; D009460:Neurologic Examination / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013777:Tetrazoles / Q000627:therapeutic use*; D013778:Tetrazolium Salts; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; C077793:candesartan cilexetil