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《Chinese Pharmacological Bulletin》 2008-03
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Effects of candesartan on aorta oxidative stress-LOX-1 pathway in salt-loaded stroke-prone spontaneously hypertensive rats

YU Yi1,WU Ke-gui2,WAN Jian-xin2,WANG Hua-jun2,ZHOU Li-na1 (1.Fuzhou General Hospital of Nanjing Military Command,Fuzhou 350025,China; 2.The First Clinical Medical College of Fujian Medical University,Fuzhou 350001,China)  
Aim To investigate the effects of an angiotensin Ⅱ receptor blocker,candesartan, on aorta oxidative stress-LOX-1 pathway in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP).Methods 12-week-old salt-loaded SHRSP were treated with candesartan(1.0 mg·kg-1·d-1)or a diuretic, trichlormethiazide(TCM,1.6 mg·kg-1·d-1) or no treatment(n=6) in each for 2 weeks. Age-matched salt-loaded WKY rats were served as control(n=6).Systolic blood pressure(SBP)was measured weekly throughout the 2-week period by means of the tail-cuff method.Thoracic aortas were extracted and 24 h urine was collected.NAD(P)H oxidase subunits(p22 phox, p47 phox and gp91 phox)mRNA expression in aorta were assayed by real-time PCR. LOX-1 and type Ⅳ collogen mRNA expression were examined by RT-PCR. gp91 phox and LOX-1 protein expression in aorta were assayed by immunohistochemistry.Urinary albumin excretion was examined by ELISA.Results At the end of the 2nd week, SBP was significantly higher in salt-loaded SHRSP than that in salt-loaded WKY rats. Treatment with candesartan and TCM significantly decreased SBP in salt-loaded SHRSP at similar levels.NAD(P)H oxidase subunits (p47 phox and gp91 phox)and LOX-1 mRNA expression in aorta were markedly higher in salt-loaded SHRSP than those in salt-loaded WKY rats.Candesartan and TCM had the effect of reducing the systolic blood pressure at similar levels. Candesartan significantly down-regulated aorta p22 phox, gp91 phox,LOX-1 and type Ⅳ collogen mRNA expression and decreased urine albumin excretion in salt-loaded SHRSP(P0.01), whereas TCM had no such effects. Also, immunohistochemistry showed the positive area and the strength of gp91 phox and LOX-1 expression in aorta decreased in candesartan treated rats than in salt-loaded SHRSP, while no immunoreactivities were found in the WKY rats.Conclusion Candesartan exerted vascular protective effects by suppressing oxidative stress-LOX-1 pathway in salt-loaded SHRSP, which might be independent of blood pressure reduction.
【Fund】: 福建省科技厅资助课题(No2000Z127)
【CateGory Index】: R544.1
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