Journal of Applied Physiology, Vol 62, Issue 3 1141-1149, Copyright © 1987 by American Physiological Society
Pulmonary pressor responses in sheep to chemically defined precursors of E. coli endotoxin
K. E. Burhop, R. A. Proctor, C. R. Raetz and J. A. Will
The toxicity of various monosaccharide and disaccharide endotoxin
precursors has now been studied in sheep. We measured the early pulmonary
arterial pressure responses after injections of the monosaccharides lipid X
(2,3-diacylglucosamine 1-phosphate) and MAGP (2-monoacylglucosamine
1-phosphate), of the tetraacyl disaccharide diphosphate precursor of lipid
A, IV-A (Federation Proc. 43: 1567, 1984), and of Escherichia coli
bacterial endotoxin (lipopolysaccharide). We also measured the response of
lipid X after prior administration of indomethacin and MAGP. Lipid X, at a
total cumulative dose of 40 micrograms/kg, produced an immediate, but
transient dose-dependent pulmonary arterial vasoconstrictive response.
MAGP, at a total dose of 40 micrograms/kg, had no pulmonary pressure
activity but did increase extravascular lung water and produce some
histological changes in the lung. Disaccharide precursor IV-A, at a total
dose of 40 micrograms/kg, produced an immediate dose-dependent pulmonary
arterial vasoconstrictive response that was prolonged for greater than 2 h.
E. coli endotoxin caused a delayed (15-min) increase in the pulmonary
arterial pressure but one that also persisted for greater than 2 h. Prior
administration of indomethacin blocked the pulmonary pressor activity of
lipid X, whereas prior administration of MAGP increased both the magnitude
and the duration of the pulmonary pressure response of lipid X. We conclude
that the initial pulmonary hypertension seen after lipid X injection may
involve cyclooxygenase-dependent formation of prostaglandins and that the
genesis of this pulmonary pressor activity is at least in part dependent on
the ester-linked hydroxymyristoyl moiety at position 3 of the lipid X
molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
