Enhanced expression of inducible nitric oxide synthase without vasodilator effect in chronically infected lungs
Department of Human Anatomy and Physiology, University College, Dublin 2, Ireland We hypothesized that abnormal ventilation-perfusion matching in chronically infected lungs was in part due to excess nitric oxide (NO) production after upregulation of inducible NO synthase (iNOS) expression. Rats were...
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Published in | American journal of physiology. Lung cellular and molecular physiology Vol. 277; no. 3; pp. 616 - L627 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.09.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Department of Human Anatomy and Physiology, University College,
Dublin 2, Ireland
We hypothesized
that abnormal ventilation-perfusion matching in chronically infected
lungs was in part due to excess nitric oxide (NO) production after
upregulation of inducible NO synthase (iNOS) expression. Rats were
anesthetized and inoculated intratracheally with
Pseudomonas aeruginosa incorporated
into agar beads (chronically infected) or with sterile agar beads
(placebo inoculated) and killed 10-15 days later.
Immunohistochemistry demonstrated increased expression of iNOS and
reduced expression of endothelial NOS (eNOS) in chronically infected
compared with placebo-inoculated or noninoculated lungs. In isolated
lungs from chronically infected rats, NOS inhibition with
N -nitro- L -arginine
methyl ester increased the mean perfusion pressure (14.4 ± 2.7 mmHg) significantly more than in the placebo-inoculated (4.8 ± 1.0 mmHg) or noninoculated (5.3 ± 0.8 mmHg) lungs
( P < 0.01). Although the chronically
infected lungs were more sensitive to NOS inhibition, further evidence
suggested that the increased iNOS expression was not associated with
enhanced iNOS activity. Selective inhibitors of iNOS did not produce an
increase in vascular resistance similar to that produced by
nonselective inhibitors. Accumulation of nitrate/nitrite in the
perfusate of isolated lungs was unchanged by chronic infection. Thus
although iNOS expression was increased in chronic pulmonary infection,
iNOS activity in the intact lung was not. Nonetheless, endogenous NO
production was essential to maintain normal vascular resistance in
these lungs.
pulmonary vascular resistance; hypoxia; Pseudomonas aeruginosa ; aminoguanidine; nitrate; nitrite |
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ISSN: | 1040-0605 0002-9513 1522-1504 |
DOI: | 10.1152/ajplung.1999.277.3.L616 |