Affiliation:
1. 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.
Abstract
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 α-actin (3.6 times;
P
<0.05), but the expression of cardiac α-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 α-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 α-actin, which suggests that, in this model, reexpression of a fetal gene can be activated by pressure overload independently of cardiac hypertrophy.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
30 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献