(Hypertension. 1999;33:961-968.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Effects of Candesartan and Cilazapril on Rats With Myocardial Infarction Assessed by Echocardiography
From the First Department of Internal Medicine (M.Y., K.T., T.O., H.Y., I.T., M.T., K.A., J.Y.) and Department of Pharmacology (S.K., H.I.), Osaka City University Medical School, Osaka, Japan.
Correspondence to Minoru Yoshiyama, MD, First Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. E-mail myoshiyama{at}med.osaka-cu.ac.jp
Abstract—The purpose of
this study was to compare the angiotensin II type 1
receptor antagonist candesartan cilexitil (candesartan) and
the angiotensin-converting enzyme inhibitor
cilazapril on cardiac function, assessed by Doppler
echocardiography and cardiac gene expression
associated with cardiac remodeling, in rats with myocardial infarction.
Candesartan or cilazapril was administered after myocardial infarction.
At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA
expression in noninfarcted myocardium were
analyzed. Candesartan and cilazapril equally prevented
increases in hypertrophy in noninfarcted
myocardium, left ventricular dilatation, and
ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the
rate of E-wave deceleration, measures of diastolic
function, increased to 9.2±0.6 and 26.3±2.6 m/s2 at 1
week after myocardial infarction. Candesartan and cilazapril,
administered at a dose of 1 mg/kg per day, prevented increases in
E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4
weeks. Candesartan and cilazapril significantly suppressed
increased mRNA expression of ß-myosin heavy chain, 
-skeletal
actin, and atrial natriuretic peptide in noninfarcted
ventricle at 1 and 4 weeks and expression of collagen I and III at 4
weeks to a similar extent. When given at a dose of 10 mg/kg per day,
both candesartan and cilazapril prevented cardiac dysfunction and gene
expression to the same extent as when given at 1 mg/kg per day. In
conclusion, Doppler echocardiography showed
that candesartan and cilazapril equally improved systolic and
diastolic function and that ventricular
remodeling accompanied modulation of cardiac gene expression.
Key Words: ventricular remodeling • myocardial infarction • receptors, angiotensin • echocardiography • genes • diastole
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