Background
Emerging data suggest a gender dimorphism in resistance and susceptibility to distant
organ injury after mechanical and thermal trauma. The aim of this study was to determine
the role that testosterone and estradiol play in modulating resistance or susceptibility
to distant organ injury, and whether their effects were associated with differences
in the production of nitric oxide.
Methods
Adult male, female, castrated male, and ovariectomized female Sprague-Dawley rats
were given intraperitoneal pentobarbital sodium anesthesia and subjected to trauma/sham
shock or trauma/hemorrhagic shock (T/HS). A second set of animals were subjected to
a 40% total body surface area, third-degree burn or sham burn. At 3 hours after resuscitation,
plasma levels of nitrite/nitrate were measured, and the extent of lung injury (permeability
to Evans Blue dye and neutrophil sequestration by myeloperoxidase) and intestinal
injury (morphology) were determined.
Results
Proestrus females showed resistance to lung and gut injury after both T/HS and burns,
and had low levels of nitrite/nitrate production. This resistance to injury was abrogated
by ovariectomy with an associated increase in nitric oxide production. Males showed
increased lung and gut injury after both T/HS and burns associated with increased
production of nitrite/nitrate. Castration decreased susceptibility to both lung and
gut injury, and decreased production of nitrite/nitrate. A correlation was noted between
intestinal and lung injury, and both intestinal and lung injury correlated with plasma
nitrite/nitrate levels.
Conclusions
Male sex hormones potentiate, while female hormones reduce T/HS and burn-induced lung
and gut injury. Production of nitric oxide is associated with increased lung and gut
injury after T/HS and burns.
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Article info
Publication history
Accepted:
April 29,
2004
Newark, NJFootnotes
Supported by NIH grant GM59841.
Identification
Copyright
© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.