Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under normal salt diet
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چکیده
Primary aldosteronism causes severe hypertension in human (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 (ENaC-/-Tg) that is normotensive under normal salt diet, but exhibits chronic hyperaldosteronism. 16 months old transgenic rescue mice which 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 to 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 (PDamil) 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.
منابع مشابه
Chronic hyperaldosteronism in a transgenic mouse model fails to induce cardiac remodeling and fibrosis under a normal-salt diet.
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 obt...
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