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Am J Physiol Lung Cell Mol Physiol (May 23, 2003). doi:10.1152/ajplung.00264.2002
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Submitted on August 6, 2002
Accepted on May 15, 2003

Inhaled Nitric Oxide Increases Surfactant Protein Gene Expression in the Intact Lamb

Regan B. Stuart1*, Boaz Ovadia1, Vincent V. Suzara1, Patrick A. Ross1, Stephan Thelitz2, Jeffrey R. Fineman3, and Jorge A. Gutierrez1

1 Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA
2 Department of Surgery, University of California, San Francisco, San Francisco, CA, USA
3 Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA; The Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: rstuart{at}itsa.ucsf.edu.

Inhaled nitric oxide (iNO) is used to treat a number of disease processes. Although in vitro data suggests that nitric oxide (NO) alters surfactant protein gene expression, the effects in vivo have not been studied. The objective of this study was to evaluate the effects of iNO on surfactant protein A, B, and C gene expression in the intact lamb. Thirteen 4-week-old lambs were mechanically ventilated with 21% oxygen, and received iNO at 40 ppm (n=7) or vehicle gas (n=6) for 24 hours. Peripheral lung biopsies were obtained at 0, 12, and 24 hours and analyzed for surfactant mRNA, protein, and total DNA content. Inhaled NO increased SP-A and SP-B mRNA content by 80% from time 0-12 hours, and by 78% and 71% respectively from time 0-24 hours. There was an increase in SP-A and SP-B protein content by 45% from time 0-12 hours, and a decrease by 70% and 65% respectively from 0-24 hours. DNA content was unchanged. The mechanisms and physiological effects of these findings warrant further investigation.




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