Abstract |
Previous studies have shown that estrogen treatment protects the heart from reperfusion injury. The adverse effects of long-term estrogen treatment limit its clinical use and emphasize the need for the development of specific pharmacological interventions such as pathway-selective estrogen receptor (ER) ligands. Pathway-selective ER ligands are compounds that retain estrogen's anti-inflammatory ability, but they are devoid of conventional estrogenic action. In the present study, the pathway-selective ER ligand WAY-169916 was assessed for its cardioprotective potential in an in vivo model of ischemia-reperfusion injury. Anesthetized, ovariectomized rabbits were administered WAY-169916 (1 mg/kg), 17beta-estradiol (E2; 20 microg/rabbit), or vehicle intravenously 30 minutes before a 30-minute occlusion and 4 hours of reperfusion. Acute treatment with either WAY-169916 or E2 resulted in a decrease in infarct size, expressed as a percent of area at risk (WAY-169916, 21.2 +/- 3.3; P < 0.001 and E2, 18.8 +/- 1.7; P < 0.001) compared with vehicle 59.4 +/- 5.4). Pretreatment with estrogen receptor antagonist ICI 182,780 significantly limited the infarct size sparing effect of both WAY-169916 and E2 when expressed as a percent of the risk region (WAY 169916, 47.4 +/- 4.4; E2, 53.01 +/- 5.0). The results demonstrate that WAY-169916 protects the heart against ischemia-reperfusion injury through an ER-dependent mechanism.
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Authors | Erin A Booth, Marta Marchesi, Andrea K Knittel, Edward J Kilbourne, Benedict R Lucchesi |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 49
Issue 6
Pg. 401-7
(Jun 2007)
ISSN: 0160-2446 [Print] United States |
PMID | 17577105
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Estrogen Antagonists
- Ligands
- Pyrazoles
- Receptors, Estrogen
- Selective Estrogen Receptor Modulators
- WAY-169916
- Fulvestrant
- Estradiol
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Topics |
- Animals
- Disease Models, Animal
- Estradiol
(administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
- Estrogen Antagonists
(pharmacology)
- Female
- Fulvestrant
- Ligands
- Myocardial Infarction
(etiology, metabolism, pathology, prevention & control)
- Myocardial Ischemia
(complications, metabolism, pathology)
- Myocardial Reperfusion Injury
(complications, metabolism, pathology)
- Myocardium
(metabolism, pathology)
- Ovariectomy
- Pyrazoles
(administration & dosage, pharmacology, therapeutic use)
- Rabbits
- Receptors, Estrogen
(antagonists & inhibitors, metabolism)
- Selective Estrogen Receptor Modulators
(administration & dosage, pharmacology, therapeutic use)
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