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This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/F1178    most recent 00386.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Wang, Q. Articles by Hummler, E. Search for Related Content PubMed PubMed Citation Articles by Wang, Q. Articles by Hummler, E.

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

¹Division of Hypertension, University Hospital, University of Lausanne, 1011 Lausanne; ²Department of Pathology, University Hospital, University of Geneva, 1211 Geneva; and ³Department of Pharmacology and Toxicology, University of Lausanne, 1005 Lausanne, Switzerland

Submitted 31 October 2003 ; accepted in final form 27 January 2004

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 (-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--skeletal and -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.

cardiac hypertrophy and fibrosis; epithelial Na channel activity; hypertension

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