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PMID: 3553241 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats.

The Journal of clinical investigation ·Vol. 79 ·No. 5 ·1987-05-00 ·Pages 1498-509

Chang SW, Feddersen CO, Henson PM, Voelkel NF

Abstract

Within 20 min after intraperitoneal injection of Salmonella enteritidis endotoxin in rats, blood platelet-activating factor (PAF) increased from 4.3 +/- 1.3 to 13.7 +/- 2.0 ng/ml (P less than 0.01) and lung PAF from 32.3 +/- 4.9 to 312.3 +/- 19.6 ng (P less than 0.01), but not lung lavage PAF. We tested the effect of PAF receptor antagonists, CV 3988 and SRI 63-441, on endotoxin-induced hemodynamic changes and lung vascular injury. Pretreatment with CV 3988 attenuated systemic hypotension, preserved hypoxic pulmonary vasoconstriction, and prolonged survival of awake catheter-implanted endotoxin-treated (20 mg/kg) rats. Pretreatment with SRI 63-441 prevented the depressed hypoxic pulmonary vasoconstriction after low dose (2 mg/kg) endotoxin. Both CV 3988 and SRI 63-441 blocked the increased extravascular accumulation of 125I-albumin and water in perfused lungs isolated from endotoxin-treated rats. We conclude that PAF is produced in the lung during endotoxemia and may be an important mediator of the systemic and pulmonary hemodynamic changes as well as the acute lung vascular injury after endotoxemia.

MeSH Terms
Animals Blood Pressure/drug effects Endotoxins/pharmacology Hemodynamics/drug effects Lung/drug effects Male Neutropenia/chemically induced Phospholipid Ethers Platelet Activating Factor/physiology Pulmonary Circulation/drug effects Quinolinium Compounds/pharmacology Rats Rats, Inbred Strains Salmonella enteritidis Thiazoles/pharmacology Time Factors Vasoconstriction/drug effects Vinblastine/pharmacology
Chemicals
Endotoxins Phospholipid Ethers Platelet Activating Factor Quinolinium Compounds Thiazoles SRI 63-441 Vinblastine CV 3988
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chang S W
Feddersen C O
Henson P M
Voelkel N F
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52 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112980
Published
1987-05-00
Pages
1498-509
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC424426
Subset
IM
Grants
NHLBI NIH HHS · HL-14985 · United States
External Links
PubMed source DOI: 10.1172/JCI112980 PMC Full Text View journal details
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