Chronic hypoxia upregulates endothelial and inducible nitric oxide
synthase gene and protein expression in rat lung.
Cras, Timothy D. Le, Chun Xue, Appavoo Rengasamy, and Roger A. Johns.
Department of Anesthesiology, University of Virginia,
Charlottesville, Virginia 22908
APStracts 2:0202L, 1995.
The effect of chronic hypoxia-induced pulmonary hypertension on nitric
oxide synthase (NOS) in the lung is controversial. To clarify the
regulation of endothelial and inducible NOS (eNOS and iNOS)
expression in the chronically hypoxic lung, Northern and Western blot
analyses were performed on mRNA and total protein from lungs of rats
exposed to three weeks of hypoxia (10% O2, normobaric) or normoxia.
Expression of the mRNA and protein for eNOS was significantly
increased (1.6 -fold and 2.1-fold, respectively) by hypoxia.
Immunohistochemistry with an isoform-specific antibody demonstrated
de novo expression of eNOS in the endothelium of resistance vessels
in the pulmonary vasculature of the hypoxic rats. eNOS was detected
in the endothelium of large vessels in both normoxic and hypoxic rat
lungs. The level of mRNA and protein for iNOS was also found to be
significantly increased (1.9-fold and 1.4-fold, respectively). In
addition to the 4.4 Kb iNOS mRNA species, a novel 4.0 Kb species was
also induced by hypoxia. We conclude that expression of eNOS and iNOS
was increased in the lungs of rats subjected to chronic hypoxia, and
that there was de novo expression of eNOS protein in the
microvascular endothelium.
Received 11 August 1995; accepted in final form 20 October 1995.
APS Manuscript Number L250-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95