Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia 22908 Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endot...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2002-06, Vol.282 (6), p.1272-L1278
Main Authors: Leuwerke, Shari M, Kaza, Aditya K, Tribble, Curtis G, Kron, Irving L, Laubach, Victor E
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Bromodeoxyuridine
Cell Division
Enzyme Inhibitors - pharmacology
Female
Lung - cytology
Lung - drug effects
Lung - enzymology
Lung - growth & development
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NG-Nitroarginine Methyl Ester - pharmacology
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase - deficiency
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Organ Size - physiology
Pneumonectomy
Pulmonary Alveoli - cytology
Regeneration - physiology
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Summary:Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia 22908 Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator of vascular endothelial growth factor-induced angiogenesis, which should necessarily occur during compensatory lung growth. Thus our hypothesis is that eNOS is critical for compensatory lung growth. To test this, left pneumonectomy was performed in eNOS-deficient mice (eNOS / ), and compensatory growth of the right lung was characterized throughout 14 days postpneumonectomy and compared with wild-type pneumonectomy and sham controls. Compensatory lung growth was severely impaired in eNOS / mice, as demonstrated by significant reductions in lung weight index, lung volume index, and volume of respiratory region. Also, pneumonectomy-induced increases in alveolar surface density and cell proliferation were prevented in eNOS / mice, indicating that eNOS plays a role in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type mice treated with the nitric oxide synthase inhibitor N G -nitro- L -arginine methyl ester. Together, these results indicate that eNOS is critical for compensatory lung growth. angiogenesis; pulmonary regeneration; pneumocytes; alveolar proliferation
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00490.2001