AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 635-L641, Copyright © 1994 by American Physiological Society
Nitric oxide synthase type I and type III gene expression are developmentally regulated in rat lung
A. J. North, R. A. Star, T. S. Brannon, K. Ujiie, L. B. Wells, C. J. Lowenstein, S. H. Snyder and P. W. Shaul
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
The successful transition from fetal to neonatal life involves a marked
decline in pulmonary vascular resistance which is modulated in part by
endothelium-derived nitric oxide. To define the molecular processes which
prepare the pulmonary circulation for nitric oxide mediation of
vasodilatation at the time of birth, we determined the ontogeny of
endothelial nitric oxide synthase (NOS-III) gene expression in lungs from
fetal and newborn rats. Maturational changes in lung neuronal NOS (NOS-I)
expression were also investigated; the latter isoform has been localized to
rat bronchiolar epithelium. NOS proteins were examined by immunoblot
analysis, and mRNA abundance was assessed in reverse
transcription-polymerase chain reaction assays. Both NOS-III and NOS-I
protein were detectable in 16-day fetal lung, they increased 3.8- and
3.1-fold, respectively, to maximal levels at 20 days of gestation (term =
22 day), and they fell postnatally (1-5 days). In parallel with the
findings for NOS-III protein, NOS-III mRNA increased from 16 to 20 days
gestation and fell after birth. In contrast, NOS-I mRNA abundance declined
during late fetal life and rose postnatally. These findings were confirmed
by Northern analyses. Thus NOS-III and NOS-I gene expression are
developmentally regulated in rat lung, with maximal NOS-III and NOS-I
protein present near term. The regulation of pulmonary NOS-III may
primarily involve alterations in transcription or mRNA stability, whereas
NOS-I expression in the maturing lung may also be mediated by additional
posttranscriptional processes.
