Candesartan inhibits sinoaortic denervation-induced cardiovascular hypertrophy in rats.
Abstract
AIM: 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.
CONCLUSION: 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.
Keywords:
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.
CONCLUSION: 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.