Mechanism of salutary effects of estrogen on cardiac function following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

Abstract

OBJECTIVES:

Because administration of 17beta-estradiol following trauma-hemorrhage improves cardiovascular responses, we investigated whether the salutary effects of 17beta-estradiol on cardiac function are mediated via Akt-dependent heme oxygenase-1 up-regulation under those conditions.

DESIGN:

Experimental animal study.

SETTING:

University laboratory.

SUBJECTS:

Male Sprague-Dawley rats.

INTERVENTIONS:

Rats underwent trauma-hemorrhage (mean blood pressure approximately 40 mm Hg for 90 mins) followed by fluid resuscitation. Before resuscitation, rats received either vehicle, 17beta-estradiol (1 mg/kg), or 17beta-estradiol plus the phosphoinositide 3-kinase inhibitor wortmannin (1 mg/kg). At 2 hrs after trauma-hemorrhage or sham operation, the rats were killed.

MEASUREMENTS AND MAIN RESULTS:

Cardiac function, heart tissue myeloperoxidase activity, cardiac and circulatory cytokine levels, cardiac intercellular adhesion molecule-1, and chemokine levels were measured. Cardiac Akt and heme oxygenase-1 were also determined. We found that 17beta-estradiol prevented the trauma-hemorrhage-induced impairment in cardiac function and increase in cardiac myeloperoxidase activity. Cardiac and systemic interleukin-6 and tumor necrosis factor-alpha levels as well as cardiac intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant-1, and macrophage inflammatory protein-2 contents were increased following trauma-hemorrhage, which were normalized by 17beta-estradiol. Administration of 17beta-estradiol following trauma-hemorrhage restored cardiac Akt phosphorylation and further increased heme oxygenase-1 expression. Coadministration of wortmannin following trauma-hemorrhage abolished the previous effects by 17beta-estradiol.

CONCLUSIONS:

These results suggest that the 17beta-estradiol-meditated improvement in cardiac function following trauma-hemorrhage occurs via Akt-dependent heme oxygenase-1 up-regulation.

• Authors: Jun-Te Hsu, Wen-Hong Kan, Chi-Hsun Hsieh, Mashkoor A Choudhry, Kirby I Bland, Irshad H Chaudry
• Journal: Critical care medicine (Crit Care Med) Vol. 37 Issue 8 Pg. 2338-44 (Aug 2009) ISSN: 1530-0293 [Electronic] United States
• PMID: 19531952 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Androstadienes
• Chemokines
• Cytokines
• Estrogens
• Protein Kinase Inhibitors
• Estradiol
• Peroxidase
• Heme Oxygenase-1
• Proto-Oncogene Proteins c-akt
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Chemokines (metabolism)
• Cytokines (metabolism)
• Estradiol (pharmacology)
• Estrogens (pharmacology)
• Heart (drug effects)
• Heme Oxygenase-1 (metabolism)
• Male
• Peroxidase (metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (drug therapy)
• Up-Regulation
• Wortmannin