AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 6 667-L678, Copyright © 1994 by American Physiological Society
Distribution of NOS in normoxic vs. hypoxic rat lung: upregulation of NOS by chronic hypoxia
C. Xue, A. Rengasamy, T. D. Le Cras, P. A. Koberna, G. C. Dailey and R. A. Johns
Department of Anesthesiology, University of Virginia, Charlottesville 22908.
Expression and localization of nitric oxide synthase (NOS) in the lungs of
chronically hypoxic and normoxic rats were studied using both
immunohistochemistry and NADPH diaphorase (NADPH-d) staining techniques. In
the normoxic and in the hypoxic rat, NOS was detected by both methods in
the endothelium of large pulmonary vessels and in the epithelium of bronchi
and bronchioli. NOS expression was not detected in the endothelium of
normoxic pulmonary resistance vessels but was prominently expressed in the
endothelium of these vessels after 2-4 wk of chronic hypoxia. In contrast
to small pulmonary vessels, the endothelium of small bronchial vessels
exhibited NOS immunostaining in both normoxic and hypoxic lungs. Hypoxia
was also found to induce de novo NOS expression in the smooth muscle of
large and small pulmonary vessels and in bronchial smooth muscle. NOS
enzyme activity in lung homogenates was assessed by [3H]arginine to
[3H]citrulline conversion. The activity of soluble NOS, but not particulate
NOS, was increased in the hypoxic lungs. These results demonstrate chronic
hypoxia-induced upregulation of NOS protein expression and activity in the
rat lung, suggesting a potentially important role of nitric oxide in
adaptation of the pulmonary circulation to chronic hypoxia. The lack of
immunostaining in small pulmonary resistance vessels is also consistent
with physiological studies suggesting that NO may not be involved in the
mechanism for maintaining the normally low pulmonary vascular resistance.
