Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading.
To determine the extent to which dietary sodium modulates aldosterone-induced cardiovascular damage, and to determine whether increased dietary potassium can prevent this damage, we used the Nomega-nitro-L-arginine methyl ester (L-NAME)/angiotensin II (Ang II) rat model of cardiac injury. This model is dependent on the presence of aldosterone for the occurrence of myocardial damage. Two sets of experiments were performed. In the first set, the following groups were studied: (1) 1% NaCl to drink (control group); (2) L-NAME/Ang II with water to drink (low salt group); (3) L-NAME/Ang II/1% NaCl (high salt group); (4) L-NAME/Ang II/1% NaCl/eplerenone (eplerenone group). Systolic blood pressure increased similarly in all groups compared with controls. Compared with the controls, the high salt group, but not the low salt or eplerenone groups, developed significant myocardial damage. In the second set of experiments three groups of animals were studied: (1) L-NAME/Ang II/1%NaCl (high salt group) (2) L-NAME/Ang II/1%NaCl/eplerenone (eplerenone group), and (3) L-NAME/Ang II/1%NaCl with an extra 1% KCl in food (high dietary potassium group). Eplerenone, but not dietary potassium supplementation, prevented the development of cardiac damage. Thus, mineralocorticoid receptor antagonist treatment and low sodium diet were effective in preventing cardiac damage, which suggests that a minimal level of aldosterone and a moderately high sodium diet are both required for the development of the cardiovascular damage in the L-NAME/Ang II model. The inability of potassium supplementation to reduce myocardial damage suggests that eplerenone's protective effect is not due to its potassium-sparing ability, but is rather related to some other feature of its selective aldosterone antagonism.
Martinez
Diego V
DV
Endocrinology-Hypertension Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Rocha
Ricardo
R
Matsumura
Mamiko
M
Oestreicher
Eveline
E
Ochoa-Maya
Margarita
M
Roubsanthisuk
Weranuj
W
Williams
Gordon H
GH
Adler
Gail K
GK
D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000009:adverse effects; D000818:Animals; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D000077545:Eplerenone; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects; D011188:Potassium / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester