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(Hypertension. 1999;34:1197.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Carvedilol and Lacidipine Prevent Cardiac Hypertrophy and Endothelin-1 Gene Overexpression After Aortic Banding
From the Departments of Cardiovascular Physiology (P-E.M., G.R.H.) and Experimental Pharmacology (J.K., T.G., M.W.), Université Catholique de Louvain, Brussels; and the Division of Endocrinology and Internal Medicine (J.D.), University Hospital of Mont-Godinne, Yvoir, Belgium.
Correspondence to Prof Maurice Wibo, Université Catholique de Louvain, Laboratoire de Pharmacologie, UCL 54.10, Ave Hippocrate 54, B-1200 Brussels, Belgium. E-mail wibo{at}farl.ucl.ac.be
Abstract—Carvedilol and
lacidipine have been shown to exert cardioprotective effects in rat
models of chronic hypertension. We investigated their effects in an
acute model of pressure overload produced by suprarenal aortic
constriction, in which enhanced myocardial production of
endothelin-1 could play a crucial role. In the absence of drug
treatment, after 1 week, aortic banding provoked an increase in carotid
pressure associated with left ventricular
hypertrophy (29%; P<0.01). These changes
were accompanied by increased myocardial expression of
preproendothelin-1 (2.5 times; P<0.05) and skeletal
-actin (3.6 times; P<0.05), but the expression of
cardiac -actin was not modified. Oral administration of carvedilol
at a dose of 30 mg · kg-1 · d-1
to rats with aortic banding normalized carotid pressure and left
ventricular weight as well as preproendothelin-1 and
skeletal -actin gene expression. Carvedilol at a lower dose (7.5
mg · kg-1 · d-1) and lacidipine
1 mg · kg-1 · d-1 had only
moderate and nonsignificant effects on carotid pressure but largely
prevented left ventricular hypertrophy
(P<0.01) and preproendothelin-1 overexpression
(P<0.05). Labetalol (60 mg ·
kg-1 · d-1) tended to exert similar
effects but insignificantly. These results show that the
antihypertrophic properties of carvedilol and lacidipine are partly
independent of their antihypertensive effects and may be related to
their ability to blunt myocardial preproendothelin-1 overexpression.
Moreover, carvedilol at a dose of 7.5 mg ·
kg-1 · d-1 did not prevent myocardial
overexpression of skeletal -actin, which suggests that, in this
model, reexpression of a fetal gene can be activated by
pressure overload independently of cardiac hypertrophy.
Key Words: endothelin • hypertrophy, left ventricular • hypertension, experimental • -actin • carvedilol • lacidipine
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