Compensatory lung growth in NOS3 knockout mice suggests synthase isoform redundancy

Stefan Pokall, Arturo R. Maldonado, Charles A. Klanke, Shuichi Katayama, Lee M. Morris, Jose F. Vuletin, Foong Yen Lim, Timothy M. Crombleholme

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Nitric oxide synthase 3 (NOS3) produces nitric oxide (NO) in endothelial cells, which stimulates cyclic guanosine monophosphate (cGMP) production and thereby mediates pulmonary vasodilation. Inhibition of cGMP enzymatic cleavage by sildenafil might be involved in lung growth stimulating processes in pulmonary hypoplasia. The aim of this study was to discover insights into the transcriptional regulation of NOS3 in a mouse model of compensatory lung growth (CLG). CLG was studied in wild type animals (WT) and NOS3 knockout mice (NOS3-/-) by dry weight, DNA, and protein quantification as well as relative quantification of NOS mRNA. All assessments were done on adult female mice, 10 days after left pneumonectomy (PNX) or sham thoracotomy. Weight ratios of right NOS3-/-) lungs were no different than controls. There was a compensatory increase in DNA and a noncompensating increase in protein ratios in NOS3-/-) mice compared with controls. Pharmacological knockdown with the pan-NOS inhibitor l-NAME (nitro-arginine methyl ester) reduced CLG by only 8% compared with the d-NAME treated control mice. Relative quantification of lung mRNA revealed no up-regulation of NOS3 expression in WT lungs after PNX, but NOS3-/-) lungs showed a 2.6-fold higher inducible NOS2 expression compared with shams. These data suggest that NOS3 loss of function alone does not impair CLG in mice, possibly because of redundancy mechanisms involving NOS2.

Original languageEnglish (US)
Pages (from-to)148-156
Number of pages9
JournalEuropean Journal of Pediatric Surgery
Volume22
Issue number2
DOIs
StatePublished - 2012

Keywords

  • compensatory lung growth
  • lung growth
  • nitric oxide
  • nitric oxide synthase

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

Fingerprint Dive into the research topics of 'Compensatory lung growth in NOS3 knockout mice suggests synthase isoform redundancy'. Together they form a unique fingerprint.

Cite this