Effects of long-term treatment with candesartan on organ damages in sinoaortic denervated rats.
The study was designed to observe the effects of long-term treatment with candesartan cilexetil (candesartan) on blood pressure (BP), blood pressure variability (BPV), baroreflex sensitivity (BRS) and end-organ damage (EOD) in sinoaortic denervated (SAD) rats. Candesartan was mixed in rat chow at an estimated dose of 3 mg/kg/day. After 12 weeks of drug administration, rats were instrumented to determine BP, BPV and BRS in conscious state. Organ damage was estimated by observation of morphologic changes. When compared with sham-operated rats, SAD rats exhibited increased BPV, decreased BRS, and normal BP and plasma angiotensin II level. Left ventricular and aortic hypertrophies and renal lesion were found in SAD rats. Candesartan significantly decreased BP and BPV, ameliorated impaired BRS, increased plasma angiotensin II level and obviously diminished the EOD in SAD rats. Multiple-regression analysis shows that decrease in left ventricular hypertrophy was mainly related to decrease in systolic BPV. Decrease in aortic hypertrophy was mainly determined by increase in BRS and decrease in systolic BP. Amelioration in renal lesion was predicted by increase in BRS and decrease in systolic BPV. BRS was the most important determinant for renal lesion and aortic hypertrophy in SAD rats. In addition, plasma angiotensin II level was higher in candesartan-treated rats. In conclusion, long-term treatment with candesartan prevented SAD-induced organ damage. Restoration of arterial baroreflex function, decrease in BPV, and blockade of activated renin-angiotensin system may contribute to the organ protective action of candesartan in SAD rats.
Xie
He-Hui
HH
Department of Pharmacology, Basic Medical College, Second Military Medical University, Shanghai 200433, China.
Miao
Chao-Yu
CY
Liu
Jian-Guo
JG
Su
Ding-Feng
DF
D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D003714:Denervation / Q000379:methods; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000187:drug effects* / Q000294:innervation*; D013777:Tetrazoles / Q000008:administration & dosage*
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan