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Am J Physiol Lung Cell Mol Physiol (August 2, 2002). doi:10.1152/ajplung.00102.2002
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Articles in PresS, published online ahead of print August 2, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00102.2002
Submitted on April 5, 2002
Accepted on July 16, 2002

Hypothermia attenuates iNOS, CAT 1, CAT 2, and nitric oxide expression in lungs of endotoxemic rats

Philip O. Scumpia1, Paul J. Sarcia1, Vincent G. DeMarco2, Bruce R. Stevens3, and Jeffrey W. Skimming2*

1 Department of Pediatrics, University of Florida, Gainesville, FL, USA
2 Department of Pediatrics, University of Florida, Gainesville, FL, USA; Department of Child Health, University of Missouri, Columbia, MO, USA; Departmetn of Physiology, University of Missouri, Columbia, MO, USA
3 Department of Physiology & Functional Genomics, University of Florida, Gainesville, FL, USA

* To whom correspondence should be addressed. E-mail: skimmingj{at}missouri.edu.

Endotoxemia stimulates endogenous nitric oxide formation, induces transcription of arginine transporters and causes lung injury. Hypothermia inhibits nitric oxide formation and is used as a means of organ preservation. We hypothesized that hypothermia inhibits endotoxin-induced intrapulmonary nitric oxide formation and that this inhibition is associated with attenuated transcription of enzymes that regulate nitric oxide formation, such as inducible nitric oxide synthase (iNOS) and the cationic amino acid transporters 1 (CAT 1) and 2 (CAT 2). Rats were anesthetized and randomized to treatment with either hypothermia (T=18-24°C) or normothermia (T=36-38°C). Endotoxin was administered intravascularly. Concentrations of iNOS, CAT 1, and CAT 2 mRNA, iNOS protein and nitrosylated proteins were measured in lung tissue homogenates. We found that hypothermia abrogated the endotoxin-induced increase in both exhaled nitric oxide and lung tissue nitrotyrosine concentrations. Western blot analyses revealed that hypothermia inhibited iNOS, but not eNOS, protein expression in lung tissues. CAT 1, CAT 2, and iNOS mRNA concentrations were lower in the lungs of hypothermic animals. These findings suggest that hypothermia protects against intrapulmonary nitric oxide overproduction and nitric oxide-mediated lung injury by inhibiting transcription of iNOS, CAT 1, and CAT 2.




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