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Role of a selective aldosterone blocker in mice with chronic heart failure.
J Card Fail. 2004 Feb; 10(1):67-73.JC

Abstract

BACKGROUND

Spironolactone, a nonselective aldosterone blocker, has a cardioprotective effect; however, significant endocrine side effects limit its use. Eplerenone is a new selective aldosterone blocker. We investigated whether eplerenone attenuates cardiac remodeling and improves function in a mouse model of heart failure and whether coadministration of eplerenone and an angiotensin-converting enzyme inhibitor (ACEi) provides better cardioprotection than either agent alone.

METHODS AND RESULTS

C57BL/6J mice were subjected to myocardial infarction (MI) by ligating the left anterior descending coronary artery. Two weeks later, the mice were either left untreated or treated with (1) eplerenone, (2) ACEi, or (3) eplerenone plus ACEi for 12 weeks. Systolic blood pressure (SBP) was measured and echocardiography performed before MI and weekly thereafter. At the end of the study, interstitial collagen fraction (ICF) and myocyte cross-sectional area (MCSA) were examined histologically. We found that (1) eplerenone significantly improved ejection fraction and cardiac output and decreased left ventricular (LV) systolic area, LV weight, ICF, and MCSA independently of changes in SBP compared with untreated animals; (2) ACEi had similar beneficial effects, accompanied by a significant reduction in SBP; and (3) combined treatment offered limited additional benefit beyond monotherapy.

CONCLUSIONS

In mice with MI, eplerenone attenuates progression of heart failure comparably to ACEi, and its effect is independent of BP lowering.

Authors+Show Affiliations

Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202-2689, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14966777

Citation

Wang, Dahai, et al. "Role of a Selective Aldosterone Blocker in Mice With Chronic Heart Failure." Journal of Cardiac Failure, vol. 10, no. 1, 2004, pp. 67-73.
Wang D, Liu YH, Yang XP, et al. Role of a selective aldosterone blocker in mice with chronic heart failure. J Card Fail. 2004;10(1):67-73.
Wang, D., Liu, Y. H., Yang, X. P., Rhaleb, N. E., Xu, J., Peterson, E., Rudolph, A. E., & Carretero, O. A. (2004). Role of a selective aldosterone blocker in mice with chronic heart failure. Journal of Cardiac Failure, 10(1), 67-73.
Wang D, et al. Role of a Selective Aldosterone Blocker in Mice With Chronic Heart Failure. J Card Fail. 2004;10(1):67-73. PubMed PMID: 14966777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of a selective aldosterone blocker in mice with chronic heart failure. AU - Wang,Dahai, AU - Liu,Yun-He, AU - Yang,Xiao-Ping, AU - Rhaleb,Nour-Eddine, AU - Xu,Jiang, AU - Peterson,Edward, AU - Rudolph,Amy E, AU - Carretero,Oscar A, PY - 2004/2/18/pubmed PY - 2004/8/31/medline PY - 2004/2/18/entrez SP - 67 EP - 73 JF - Journal of cardiac failure JO - J. Card. Fail. VL - 10 IS - 1 N2 - BACKGROUND: Spironolactone, a nonselective aldosterone blocker, has a cardioprotective effect; however, significant endocrine side effects limit its use. Eplerenone is a new selective aldosterone blocker. We investigated whether eplerenone attenuates cardiac remodeling and improves function in a mouse model of heart failure and whether coadministration of eplerenone and an angiotensin-converting enzyme inhibitor (ACEi) provides better cardioprotection than either agent alone. METHODS AND RESULTS: C57BL/6J mice were subjected to myocardial infarction (MI) by ligating the left anterior descending coronary artery. Two weeks later, the mice were either left untreated or treated with (1) eplerenone, (2) ACEi, or (3) eplerenone plus ACEi for 12 weeks. Systolic blood pressure (SBP) was measured and echocardiography performed before MI and weekly thereafter. At the end of the study, interstitial collagen fraction (ICF) and myocyte cross-sectional area (MCSA) were examined histologically. We found that (1) eplerenone significantly improved ejection fraction and cardiac output and decreased left ventricular (LV) systolic area, LV weight, ICF, and MCSA independently of changes in SBP compared with untreated animals; (2) ACEi had similar beneficial effects, accompanied by a significant reduction in SBP; and (3) combined treatment offered limited additional benefit beyond monotherapy. CONCLUSIONS: In mice with MI, eplerenone attenuates progression of heart failure comparably to ACEi, and its effect is independent of BP lowering. SN - 1071-9164 UR - https://www.unboundmedicine.com/medline/citation/14966777/Role_of_a_selective_aldosterone_blocker_in_mice_with_chronic_heart_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1071916403005785 DB - PRIME DP - Unbound Medicine ER -