Effects of acute and chronic hypoxia on rat lung cyclooxygenase. Chida, Masayuki, and Norbert F. Voelkel. Pulmonary Hypertension Center, University of Colorado Health Science Center, Denver, Colorado 80262
APStracts 2:0227L, 1995.
Cyclooxygenase-2 (COX-2) is an inducible cyclooxygenase enzyme and may play an important role in the pathogenesis of lung injury and in pulmonary vascular remodeling. In this study we determined the effects of acute or chronic hypoxia on COX-2 induction, and its modulation by [lambda]NO and cAMP. Isolated perfused rat lungs were exposed to a normoxic gas mixture or a hypoxic gas mixture for 3 h. Northern blot analysis showed that 3 h of acute hypoxia were sufficient to increase COX-2 but not COX-1 transcripts in the lung. COX-2 expression induced by acute hypoxia was enhanced by an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methylester, and suppressed by sodium nitroprusside, meclofenamate and H-7 (an inhibitor of protein kinase-A and -C). COX-2 expression was also enhanced by dibutyryl cyclic AMP and iloprost, a prostacyclin analogue. In contrast, 2 wks of chronic hypobaric hypoxia did not enhance COX-2 expression in the lung, but increased COX-2 protein levels as assessed by Western blots. We conclude that acute hypoxia induces COX-2 gene expression in rat lungs and that COX-2 induction by acute hypoxia is modulated by [lambda]NO, cAMP and cyclooxygenase products. In particular, prostacyclin produced by the lung during hypoxia or shear stress induces lung COX-2 expression via a positive feed back mechanism. 

Received 6 March 1995; accepted in final form 7 December 1995.
APS Manuscript Number L70-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95