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《Chinese Pharmacological Bulletin》 2007-06
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Effects of candesartan on expression of the renal renin-angiotensin system in salt-loaded stroke-prone spontaneously hypertensive rats

YU Yi1, WU Ke-gui2(1.Dept of Nephrology and Hemodialysis,Fuzong Clinical Medical School,Fujian medical University, Fuzhou General Hospital of Nanjing Command; 2.Research Institute of Hypertension of Fujian, the First Affiliated Hospital, Fujian Medical University , Fuzhou 350025, China)  
Aim To investigate the effects of an angiotensin Ⅱ (Ang Ⅱ) receptor blocker(ARB), candesartan, on expression of the renal renin-angiotensin system (RAS) and its renoprotection in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) in vivo. 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 group) for 2 weeks. Age-matched salt-loaded WKY rats were served as control(n=6). Urinary albumin, protein excretion and renal Ang Ⅱ were measured with ELISA, Bradford assay and radioimmunology methods separately. The renal cortex mRNA expression of RAS components, including angiotensinogen, renin,cathepsin D,ACE, AT1R and AT2R was detected by RT-PCR. Renal cortex mRNA expression of TGF-β1, osteopontin and type Ⅳ collogen was detected with RT-PCR. Results The mRNA expression of RAS components, TGF-β1, osteopontin and type Ⅳ collogen was significantly up-regulated in salt-loaded SHRSP compared with salt-loaded WKY rats(P0.01). Renal Ang Ⅱ levels and urinary albumin and protein excretion were markedly increased in salt-loaded SHRSP(P0.01).Candesartan and TCM have the effect to reduce systolic blood pressure at similar level. Candesartan signifi-cantly downregulated mRNA levels of RAS components, TGF-β1, osteopontin and type Ⅳ collogen in salt-loaded SHRSP(P0.01)while TCM only downregulated mRNA levels of angiotensinogen, ACE, TGF-β1 and type Ⅳ collogen(P0.05). Candesartan, but not TCM, markedly decreased renal Ang Ⅱ levels and urinary albumin and protein excretion(P0.01).Conclusion Candesartan exerts renoprotective effects independently of blood pressure reduction by suppressing renal expression of RAS components in salt-loaded SHRSP.
【Fund】: 福建省科技厅资助课题(No2000Z127)
【CateGory Index】: R544.1
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