In vivo lipopolysaccharide pretreatment inhibits cgmp release from
the isolated-perfused rat lung.
Kurrek, Matt M., Warren M. Zapol, Alexandra Holzmann, Galina Filippov,
Marianne Winkler, and Kenneth D. Bloch.
From the the Department of Anaesthesia of the Beth Israel Hospital
and Department of Anesthesia and the Cardiovascular Research Center
of the General Medical Services of the Massachusetts General Hospital
and Harvard Medical School, Boston, Massachusetts
APStracts 2:0096L, 1995.
Administration of bacterial lipopolysaccharide (LPS) to rats
stimulates synthesis of nitric oxide (NO), a free radical molecule
which activates soluble guanylate cyclase, thereby increasing
intracellular cGMP concentration and inducing systemic
vasodilatation. To investigate the effect of endotoxemia on the
pulmonary NO/cGMP signal transduction system, we measured the release
of cGMP by isolated-perfused lungs of rats which received an
intraperitoneal injection of LPS (1 mg/kg) or saline two days
earlier. Over 90 minutes, 1.4+/-0.78 nmole and 0.079+/-0.016 nmole
cGMP accumulated in pulmonary perfusates of saline- and LPS-treated
rats, respectively (p<0.05). Despite addition to the perfusate
of Zaprinast, superoxide dismutase, or A23187, markedly less cGMP was
released from the lungs of rats exposed to LPS than from the lungs of
control rats. In contrast, following ventilation with 100 parts per
million NO gas, cGMP accumulating in the perfusate of the lungs of
both groups of rats was markedly increased, and the quantity of cGMP
released from the lungs of LPS-treated rats was similar to that
released by control rat lungs (2.8+/-0.57 versus 3.3+/-0.88 nmol,
p=NS). Using immunoblot techniques, equal concentrations of
constitutive endothelial NO synthase were detected in the lungs of
rats treated with saline or LPS. These results demonstrate that the
NO/cGMP signal transduction system is abnormal in the lungs of rats
exposed to LPS, at least in part, at the level of endothelial NO
synthase activation.
Received 27 December 1994; accepted in final form 1 June 1995.
APS Manuscript Number L371-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.