Eplerenone offsets cardiac and aortic adverse remodeling in spontaneously hypertensive rats.
BACKGROUND
Several studies have shown beneficial effects of eplerenone in hypertension and left ventricular dysfunction, but its action on cardiac and vascular changes secondary to blood pressure elevation are not clear yet.


METHODS
Twenty-five male spontaneously hypertensive rats (SHR) were assigned into five groups: young SHR (16 weeks), control SHR (22 weeks), and SHR treated by eplerenone (50 mg/kg/day), enalapril (10 mg/kg/day) or eplerenone+enalapril during 6 weeks. Five Wistar male rats were used as reference group. Cardiac structure and aorta were analyzed by stereology and image analysis.


RESULTS
The raise of blood pressure (202+/-3 mm Hg in control SHR) was significantly attenuated by eplerenone (169+/-2 mm Hg) or enalapril (170+/-2 mm Hg, P<0.001 versus control SHR), and more intensely by combined therapy (160+/-2 mm Hg, P<0.01 versus eplerenone or enalapril). The number of cardiomyocytes in left ventricle was preserved in enalapril group (35,660+/-910 versus 16,220+/-730x10(3) in control SHR, P<0.01) but more significantly in eplerenone, alone or combined, groups (38,380+/-439 and 38,660+/-374x10(3), respectively, P<0.001 versus control). The increased connective tissue volume density (35.8+/-1.2%) noted in the left ventricle of control SHR was significantly attenuated by eplerenone (7.4+/-0.8%), enalapril (8.0+/-0.6%) or eplerenone+enalapril (6.0+/-1.1%, P<0.01 treated versus control SHR). Media-to-lumen ratio of intramyocardial arteries was reduced by enalapril, but more significantly by eplerenone alone or combined with enalapril. The increase of media cross-sectional area of aorta in control SHR was attenuated by eplerenone and/or enalapril.


CONCLUSIONS
Eplerenone is effective in attenuating cardiovascular remodeling in SHR, confirming the important role of aldosterone in this process.
Burla
Adriana K
AK
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Centre, State University of Rio de Janeiro, Av 28 de Setembro 87 fds 20551-030 Rio de Janeiro, Rio de Janeiro, Brazil.
Neves
Mario Fritsch
MF
Oigman
Wille
W
Mandarim-de-Lacerda
Carlos A
CA
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects*; D004656:Enalapril / Q000627:therapeutic use; D000077545:Eplerenone; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects*
D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D004656:Enalapril