Effects of long-term treatment with candesartan on hemodynamics and organ damage in spontaneously hypertensive rats.
This study was designed to investigate the effects of candesartan on blood pressure (BP) and blood pressure variability (BPV) reductions, baroreflex sensitivity (BRS) amelioration, and organ protection in spontaneously hypertensive rats (SHR).


METHODS
Studies were performed in two groups of SHR (n = 13 for control rats; and n = 20 for candesartan-treated rats) and one group of WKY rats (n = 13). Candesartan (3 mg /kg/d) was given in rat chow for 4 months. BP was then continuously recorded for 24 hours in conscious state. After the determination of BRS, rats were killed for organ-damage evaluation.


RESULTS
Long-term treatment with candesartan significantly reduced BP and BPV expressed by both standard deviation and variation coefficient of BP, enhanced BRS and produced obvious organ protection. Compared with BP level, BPV and BRS values showed a closer or similar relationship with organ-damage parameters in SHR. Multiple regression analysis showed that the decrease in left ventricular hypertrophy was most closely associated with the increase in BRS, whereas the decrease in aortic hypertrophy was most closely associated with the decrease in 24-hour systolic BPV, and the amelioration in renal lesions, with the increase in BRS and the decrease in 24-hour systolic BPV.


CONCLUSIONS
long-term treatment with candesartan results in organ protection in SHR. Besides BP reduction, the decrease in BPV and the restoration of BRS are significantly related to this organ protection.
Xie
He-Hui
HH
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Chen
Yuan-Yuan
YY
Miao
Chao-Yu
CY
Shen
Fu-Ming
FM
Su
Ding-Feng
DF
D000284:Administration, Oral; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D017704:Baroreflex / Q000187:drug effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012044:Regression Analysis; D013777:Tetrazoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D013995:Time
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan