(Circulation. 1995;92:2690-2696.)
© 1995 American Heart Association, Inc.
Articles |
Cardiac Renin-Angiotensin System in the Hypertrophied Heart
From the First Department of Internal Medicine, Shiga University of Medical Sciences, Tsukinowa Seta, Ohtsu-city, Shiga-ken, Japan.
Correspondence to Naoharu Iwai, MD, First Department of Internal Medicine, Shiga University of Medical Sciences, Tsukinowa Seta, Ohtsu-city 520-21, Shiga-ken, Japan.
Background The cardiac renin-angiotensin system (RAS) has been suggested to play an important role in heart failure and cardiac hypertrophy. In the present study, we evaluated the expression of each component of the RAS in hypertrophied heart induced by aortocaval shunt.
Methods and Results The expression levels of renin,
angiotensinogen, angiotensin-converting
enzyme (ACE), and angiotensin II type Ia and Ib receptor
(AT1aR and AT1bR) mRNA were determined by the reverse
transcription–polymerase chain reaction method owing to the
relatively low expression levels of these mRNAs in the ventricle. The
expression level of renin or angiotensinogen mRNA in the
ventricle was very low, more than 1000-fold lower than that in the
kidney or liver, respectively. The expression of ACE mRNA in the
ventricle was relatively abundant and was increased in the
hypertrophied ventricle in this model, whereas no significant increases
in the expression levels of AT1aR and AT1bR mRNA were observed.
Administration of lisinopril attenuated the development of
left and right ventricular hypertrophy in this
model and was accompanied by an attenuation of the upregulation of the
ACE, collagen type I-
, and vimentin mRNAs. Because the activity of
the circulating RAS in the aortocaval shunt rats was not higher than
that in the sham-operated rats, the effects of
lisinopril in attenuating the ventricular
hypertrophy may be due to inhibition of the increased ACE
in the ventricle.
Conclusions The present study supports the importance of ACE expressed in the ventricle in the development of hypertrophy induced by aortocaval shunt.
Key Words: angiotensin • renin • receptors • genes, hypertrophy
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