Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice.
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.
Leuwerke
Shari M
SM
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Virginia 22908-1359, USA.
Kaza
Aditya K
AK
Tribble
Curtis G
CG
Kron
Irving L
IL
Laubach
Victor E
VE
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000502:physiology; D011013:Pneumonectomy; D011650:Pulmonary Alveoli / Q000166:cytology; D012038:Regeneration / Q000502:physiology
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D001973:Bromodeoxyuridine; D019331:NG-Nitroarginine Methyl Ester