Alveolar endotoxin increases alveolar liquid clearance in rats.
Garat, C., S. Rezaiguia, M. Meignan, M. P. D' Ortho, A. Harf, M. A.
Matthay, and C. Jayr.
Department of Physiology and Department of Nuclear Medicine,
H[circumflex]opital Henri Mondor, Institut National de la
Sant[acute]e et de la Recherche M[acute]edicale Unit[acute]e 296,
94010 Cr[acute]eteil, France, Department of Medicine and Anesthesia
and the Cardiovascular Research Institute, University of California,
San Francisco, CA 94143-0130, USA, Department of Anesthesia, Institut
Gustave Roussy, 94805 Villejuif, France
APStracts 2:0333A, 1995.
Under some pathological conditions, ion transport across alveolar
epithelial cells is down-regulated, whereas under other pathological
conditions, it may be up-regulated. Because endotoxin is a
biologically relevant pathological stimulus, we investigated the
effect of endotoxin on alveolar epithelial liquid clearance in vivo.
Escherichia coli endotoxin (220 [mu]g/kg) was instilled into the
lungs via the trachea of rats. Then, at 24 or 40 hours after the
endotoxin instillation, alveolar and lung liquid clearance were
studied over one hour by instilling a 5% albumin solution with 1.5
[mu]Ci of 125I-labeled albumin (6 ml/kg into both lungs). Alveolar
liquid clearance was significantly greater at both 24 h (36 +/- 5%)
and 40 h (38 +/- 7%) after endotoxin exposure compared to saline
instilled controls (27 +/- 6%). Although there was an influx of
neutrophils into the air spaces, there was no increase in lung
epithelial permeability to protein at either 24 or 40 hours.
Amiloride (2 x 10-3 M), a sodium channel inhibitor, significantly
reduced alveolar liquid clearance in the rats exposed to endotoxin.
However, the increase in alveolar liquid clearance was not inhibited
when propranolol (2 x 10-5 M) was added to the 5% albumin solution.
Thus, exposure to alveolar endotoxin up-regulates net alveolar fluid
clearance in vivo for up to 40 hours, a potentially important
mechanism for accelerating alveolar fluid clearance under some
pathological conditions. The increase in alveolar liquid clearance 24
and 40 hours following instillation of endotoxin into the air spaces
is mediated by an increased uptake of sodium through amiloride
-sensitive sodium channels.
Received 19 January 1995; accepted in final form 19 July 1995.
APS Manuscript Number A71-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.