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Medroxyprogesterone Acetate Prevents the Cardioprotective Effects of 17β‐estradiol
Author(s) -
Booth Erin A.,
Lucchesi Benedict R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a231-b
Subject(s) - medroxyprogesterone acetate , medicine , progestin , estrogen , immune system , myocardial infarction , ischemia , cardiology , hormone , cardioprotection , endocrinology , immunology
Many studies have shown protective effects of estrogen administration in models of cardiovascular disease. However, there is a discrepancy between these data and those of the recent clinical trials with hormone replacement. One possible explanation for the divergent data is the addition of progestin to the hormone regimen in both the WHI and HERS trials. The aim of the current study was to determine the effects of a combination of 17β‐estradiol (E2; 20μg) and medroxyprogesterone acetate (MPA; 80μg) on infarct size. Anesthetized male rabbits were administered vehicle, E2, or a combination of E2/MPA intravenously 30 minutes before a 30‐minute occlusion of the coronary artery and 4 hours of reperfusion. Administration of E2 30 minutes before induction of myocardial ischemia significantly reduced infarct size as a percent of the area of risk (21.7 + 5.2; P < 0.001) compared to vehicle (56.1 + 3.4). However, when combined with MPA, E2 failed to elicit a protective effect on infarct size (49.2 + 5.2). Treatment with E2 reduced serum levels of cardiac troponin‐I, immune complex deposition in myocardial tissue, and activation of the complement system. All of these effects were reversed by MPA. The results suggest that MPA antagonizes the infarct‐sparing effects of E2, possibly through modulation of the immune response after ischemia and reperfusion. Funding: Cardiovascular Research Fund, University of Michigan Medical School