17Beta-estradiol as a receptor-mediated cardioprotective agent.
Cardiac tissue that undergoes an ischemic episode exhibits irreversible alterations that become more extensive upon reperfusion. Estrogen treatment has been reported to protect against reperfusion injury, but the mechanism remains unknown. The cardioprotective effects of 17beta-estradiol, a biologically active form of the hormone, and 17alpha-estradiol were assessed in an in vivo occlusion-reperfusion model. Anesthetized, ovariectomized rabbits were administered 17beta-estradiol (20 microg), 17alpha-estradiol (1 mg), or vehicle intravenously 30 min before a 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 4 h of reperfusion. Infarct size as a percentage of area at risk decreased in the 17beta-estradiol-treated group (18.8 +/- 1.7) compared with 17alpha-estradiol (41.9 +/- 4.8; P < 0.01) or vehicle groups (48 +/- 5.5; P < 0.001). Similar results were obtained when infarct size was expressed as a percentage of total left ventricle. The second objective of the study was to assess fulvestrant (Faslodex, ICI 182,780), an estrogen receptor antagonist, for its effects on infarct size in ovariectomized female rabbits treated with 17beta-estradiol. ICI 182,780 was administered intravenously 1 h before the administration of 17beta-estradiol (20 microg) or vehicle. The hearts were subjected to 30-min LAD coronary artery occlusion and 4 h of reperfusion. Pretreatment with ICI 182,780 significantly limited the infarct size sparing effect of 17beta-estradiol when expressed as a percentage of the risk region (53.0 +/- 5.0). The results indicate that 17beta-estradiol protects the heart against ischemia-reperfusion injury and that the observed cardioprotection is mediated by the estrogen receptor.
Booth
Erin A
EA
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.
Marchesi
Marta
M
Kilbourne
Edward J
EJ
Lucchesi
Benedict R
BR
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D011960:Receptors, Estrogen / Q000819:agonists; D015427:Reperfusion Injury / Q000517:prevention & control
D002316:Cardiotonic Agents; D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol