Activation of estrogen receptor-alpha protects the in vivo rabbit heart from ischemia-reperfusion injury.

Abstract

The estrogen receptor (ER) mediates estrogenic activity in a variety of organs, including those in the reproductive, cardiovascular, immune, and central nervous systems. Experimental studies have demonstrated that 17beta-estradiol (E2) protects the heart from ischemia-reperfusion injury. Two estrogen receptors, ER alpha and ER beta, mediate the actions of estrogen; however, it is not certain which ER mediates the cardioprotective effects of E2. In the present study, the ER-selective agonists 4,4',4''-[4-propyl-(1H)-pyrazole-1,3,5-triyl]tris-phenol (PPT; ER alpha) and 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ER beta) were assessed for their cardioprotective potential in an in vivo rabbit model of ischemia-reperfusion injury. Anesthetized female rabbits were administered PPT (3 mg/kg), DPN (3 mg/kg), E2 (20 microg/rabbit), or vehicle intravenously 30 min before a 30-min occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Acute treatment with E2 (17.7 +/- 2.9%; P < 0.001) and PPT (18.1 +/- 2.9%; P < 0.001), but not DPN (45.3 +/- 2.4%) significantly decreased infarct size as a percent of area at risk compared with vehicle (45.3 +/- 2.4%). Coadministration of PPT or E2 with the ER antagonist ICI-182,780 limited the infarct size-sparing effect of the compounds (43.8 +/- 6.6% and 40.6 +/- 5.7% respectively, expressed as a percentage of risk region). PPT reduced the release of cardiac-specific troponin-I and reduced the tissue deposition of the membrane attack complex and C-reactive protein similar to that of E2. The results indicate that activation of ER alpha, but not ER beta, is required for the observed cardioprotective effects of E2.

• Authors: Erin A Booth, Nabeel R Obeid, Benedict R Lucchesi
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 289 Issue 5 Pg. H2039-47 (Nov 2005) ISSN: 0363-6135 [Print] United States
• PMID: 15994857 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,3-bis(4-hydroxyphenyl)-propionitrile
• Biomarkers
• Complement Membrane Attack Complex
• Estrogen Receptor alpha
• Estrogen Receptor beta
• Nitriles
• Phenols
• Pyrazoles
• Troponin I
• 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
• Fulvestrant
• Estradiol
• C-Reactive Protein

Topics

• Animals
• Biomarkers
• C-Reactive Protein (metabolism)
• Complement Membrane Attack Complex (metabolism)
• Estradiol (analogs & derivatives, pharmacology)
• Estrogen Receptor alpha (agonists)
• Estrogen Receptor beta (agonists)
• Female
• Fluorescent Antibody Technique
• Fulvestrant
• Heart (drug effects)
• Hemodynamics (physiology)
• In Vitro Techniques
• Myocardial Reperfusion Injury (prevention & control)
• Nitriles (pharmacology)
• Ovariectomy
• Phenols (pharmacology)
• Pyrazoles (pharmacology)
• Rabbits
• Troponin I (metabolism)