Candesartan inhibits sinoaortic denervation-induced cardiovascular hypertrophy in rats.
OBJECTIVE
To study the effect of candesartan cilexetil (candesartan), a new AT1 receptor antagonist, on sinoaortic denervation (SAD)-induced cardiovascular hypertrophy and its potential mechanisms in rats.


METHODS
For long-term treatment, candesartan (6 mg/kg/d) was given in rat food for 16 weeks after SAD surgery, and for acute treatment, a single dose of candesartan (3 mg/kg) was administrated intragastrically at 30 d after SAD.


RESULTS
The indexes of left ventricular and aortic hypertrophy in candesartan-treated SAD rats were decreased when compared with untreated SAD rats, and similar to or less than those in normal rats. SAD-induced cardiomyocyte hypertrophy, myocardial fibrosis, wall thickening of intramyocardial arterioles and aortae, and destruction of vascular internal elastin membrane were almost inhibited by candesartan. The plasma angiotensin II levels were markedly increased in treated SAD rats and negatively correlated with the indexes of hypertrophy. Both blood pressure and its variability were reduced by a single dose of candesartan during 3 h of observation period.


CONCLUSIONS
Candesartan can efficiently inhibit SAD-induced cardiovascular hypertrophy. In addition to known mechanisms, upregulation of circulating angiotensin II and stabilization of blood pressure may be involved in this cardiovascular protection of candesartan.
Miao
Chao-Yu
CY
Department of Pharmacology, Basic Medical College, Second Military Medical University, Shanghai 200433, China. cymiao@citiz.net
Xie
He-Hui
HH
Wang
Jian-Jun
JJ
Su
Ding-Feng
DF
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000294:innervation*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D006332:Cardiomegaly / Q000503:physiopathology*; D003714:Denervation / Q000009:adverse effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000294:innervation*; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan