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Articles in PresS, published online ahead of print July 3, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00112.2002
Submitted on April 15, 2002
Accepted on June 28, 2002
1 Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
2 San Antonio Military Pediatric Center, San Antonio, TX, USA
3 Southwest Foundation for Biomedical Research, San Antonio, TX, USA
4 San Antonio Military Pediatric Center, San Antonio, TX, USA; Southwest Foundation for Biomedical Research, San Antonio, TX, USA
* To whom correspondence should be addressed. E-mail: pshaul{at}mednet.swmed.edu.
Nitric oxide (NO), produced by NO synthase (NOS), plays a critical role in multiple processes in the lung during the perinatal period. To better understand the regulation of pulmonary NO production in the developing primate, we determined the cell specificity and developmental changes in NOS isoform expression and action in the lungs of third trimester fetal baboons. Immunohistochemistry in lungs obtained at 175 d gestation (term = 185 d) revealed that all three NOS isoforms, neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), are primarily expressed in proximal airway epithelium. In proximal lung, there was a marked increase in total NOS enzymatic activity from 125 to 140d gestation due to elevations in nNOS and eNOS, whereas iNOS expression and activity were minimal. Total NOS activity was constant from 140 to 175d gestation, and during the latter stage (160 to 175d gestation) a dramatic fall in nNOS and eNOS was replaced by a rise in iNOS. Studies done within 1h of delivery at 125 or 140d gestation revealed that the principal increase in NOS during the third trimester is associated with an elevation in exhaled NO levels, a decline in expiratory resistance, and greater pulmonary compliance. Thus, there are developmental increases in pulmonary NOS expression and NO production during the early third trimester in the primate which may enhance airway and parenchymal function in the immediate postnatal period.
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