Document Detail

Broiler pulmonary hypertensive responses during lipopolysaccharide-induced tolerance and cyclooxygenase inhibition.
MedLine Citation:
PMID:  19096060     Owner:  NLM     Status:  MEDLINE    
Bacterial lipopolysaccharide (LPS, endotoxin) triggers pulmonary hypertension (PH) characterized by an increase in pulmonary arterial pressure (PAP) that reaches a peak value within 20 to 25 min and then gradually subsides within 60 min. As the PAP subsides PH cannot be reinitiated, signifying the onset of a period of tolerance (refractoriness) to repeated LPS exposure. The present study was conducted to determine the duration of this tolerance, and to evaluate key mediators thought to contribute to LPS-mediated PH in broilers. Tolerance was shown to persist for 4 to 5 d after the initial exposure to LPS. In tolerant broilers supramaximal i.v. injections of LPS did not reinitiate PH, nor was a significant modulatory role for nitric oxide demonstrated. The pulmonary vasculature of tolerant broilers remains responsive to the thromboxane A(2) (TxA(2)) mimetic U44069, 5-hydroxytryptamine (5-HT, serotonin), and constitutive nitric oxide. Meclofenamate successfully blocked the conversion of arachidonic acid to vasoconstrictive eicosanoids such as TxA(2); nevertheless, meclofenamate failed to inhibit PH in response to LPS. Therefore, TxA(2) does not appear to be the primary vasoconstrictor involved in the PH response to LPS and neither does 5-HT. Broilers emerging from tolerance 5 d after the initial exposure to LPS exhibited interindividual variation in their PH responsiveness to a second LPS injection, ranging from zero response (individuals that remain fully tolerant) to large increases in PAP (post-tolerant individuals). Tolerance might be an important compensatory or protective mechanism for broilers whose pulmonary vascular capacity is marginally adequate under optimal conditions, and whose respiratory systems are chronically challenged with LPS in commercial production facilities. The key vasoconstrictors responsible for the PH elicited by LPS remain to be determined.
R F Wideman; O T Bowen; G F Erf
Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Poultry science     Volume:  88     ISSN:  0032-5791     ISO Abbreviation:  Poult. Sci.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-19     Completed Date:  2009-03-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401150     Medline TA:  Poult Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  72-85     Citation Subset:  IM    
Department of Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA.
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MeSH Terms
Cyclooxygenase Inhibitors / pharmacology*
Hypertension, Pulmonary / chemically induced,  veterinary*
Lipopolysaccharides / adverse effects*
Meclofenamic Acid / pharmacology*
Poultry Diseases
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Lipopolysaccharides; 644-62-2/Meclofenamic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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