Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under a normal-salt diet

Détails

ID Serval
serval:BIB_F802E588109A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under a normal-salt diet
Périodique
American Journal of Physiology Renal Physiology
Auteur(s)
Wang Q., Clement S., Gabbiani G., Horisberger J. D., Burnier M., Rossier B. C., Hummler E.
ISSN
0363-6127 (Print)
Statut éditorial
Publié
Date de publication
06/2004
Volume
286
Numéro
6
Pages
F1178-84
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Jun
Résumé
Primary aldosteronism causes severe hypertension in humans (Conn's syndrome) with cardiac hypertrophy, characterized by a fibrosis more severe than the one observed in patients with essential hypertension. This suggests that aldosterone by itself may have specific and direct effects on cardiac remodeling through the activation of the cardiac mineralocorticoid receptor. Experimental evidence obtained in studying uninephrectomized rats treated with aldosterone or deoxycorticosterone (DOC) together with salt loading has led to similar conclusions. To examine the direct consequences of chronically elevated aldosterone levels on cardiac pathophysiology, we analyzed a mouse model (alpha-epithelial Na channel -/-Tg) that is normotensive under normal-salt diet but exhibits chronic hyperaldosteronism. Sixteen-month-old transgenic rescue mice that were kept under a regular salt diet that contains a small amount of sodium (0.3% Na(+)) displayed a compensated PHA-1 phenotype with normal body weight, normal kidney index, normal blood pressure, but 6.3-fold elevated plasma aldosterone levels compared with the age-matched control group. Peripheral resistance of distal colon to aldosterone was shown by a significant decrease of the amiloride-sensitive rectal potential difference, and its diurnal cyclicity was blunted. Despite chronically high plasma aldosterone levels, these animals do not show any evidence of cardiac hypertrophy, remodeling, or fibrosis, using collagen staining and anti-alpha-skeletal and alpha-smooth actin immunochemical labeling of heart sections. Cardiac fibrosis as seen in DOC- or aldosterone/salt-treated animal models is therefore likely to be due to the synergistic effect of salt, aldosterone, and other confounding factors rather than to the elevated circulating aldosterone levels alone.
Mots-clé
Aging/physiology Animals Blood Pressure/physiology Cardiac Output/physiology Cardiomegaly/genetics/pathology Chronic Disease Electrophysiology Fibrosis Genotype Heart Function Tests Heart Rate/physiology Hyperaldosteronism/*genetics/*pathology Immunohistochemistry Mice Mice, Transgenic Myocardium/*pathology Reverse Transcriptase Polymerase Chain Reaction Sodium Chloride, Dietary/*pharmacology Ventricular Remodeling/*physiology
Pubmed
Web of science
Création de la notice
24/01/2008 13:38
Dernière modification de la notice
20/08/2019 17:24
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