title: Stress preconditioning attenuates oxidative injury to the alveolar epithelium of the lung following haemorrhage in rats.
abstract: Inhibition of cAMP-dependent stimulation of vectorial fluid transport across the alveolar epithelium following haemorrhagic shock is mediated by reactive nitrogen species released within the airspaces of the lung. We tested here the hypothesis that the prior activation of the cellular heat shock or stress response, via exposure to either heat or geldanamycin, would attenuate the release of airspace nitric oxide (NO) responsible for the shock-mediated failure of the alveolar epithelium to respond to catecholamines in rats. Rats were haemorrhaged to a mean arterial pressure of 30-35 mmHg for 60 min, and then resuscitated with a 4 % albumin solution. Alveolar fluid clearance was measured by change in concentration of a protein solution instilled into the airspaces 5 h after the onset of haemorrhage. Stress preconditioning restored the cAMP-mediated upregulation of alveolar liquid clearance after haemorrhage. The protective effect of stress preconditioning was mediated in part by a decrease in the expression of iNOS in the lung. Specifically, stress preconditioning decreased the production of nitrite by endotoxin-stimulated alveolar macrophages removed from haemorrhaged rats or by A549 and rat alveolar epithelial type II cell monolayers stimulated with cytomix (a mixture of TNF-alpha, IL-1beta and IFN-gamma) for 24 h. In summary, these results provide the first in vivo evidence that stress preconditioning restores a normal fluid transport capacity of the alveolar epithelium in the early phase following haemorrhagic shock by attenuating NO-mediated oxidative stress to the lung epithelium.
authors.affiliation: Laboratory of Surgical Research, Department of Anesthesia, University of California, San Francisco, CA 94143, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: L N
authors.initials: LN
authors.lastname: Lu
authors.forename: T
authors.initials: T
authors.lastname: Geiser
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: M A
authors.initials: MA
authors.lastname: Matthay
authors.forename: W J
authors.initials: WJ
authors.lastname: Welch
mesh_terms: D000818:Animals; D016227:Benzoquinones; D001692:Biological Transport / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D003213:Conditioning, Psychological; D004847:Epithelial Cells / Q000378:metabolism; D006470:Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D006358:Hot Temperature; D047029:Lactams, Macrocyclic; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000503:physiopathology; D013312:Stress, Physiological / Q000503:physiopathology*
chemical_list: D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D009569:Nitric Oxide; C001277:geldanamycin