The NO donor molsidomine reduces endothelin-1 gene expression in chronic
hypoxic rat lungs.
Blumberg, Friedrich C., Konrad Wolf, Peter Sandner, Cornelia Lorenz, Günter A. J.
Riegger, and Michael Pfeifer.
1Department of Internal Medicine II and 2Institute of Physiology, University of
Regensburg, 93042 Regensburg, Germany
APStracts 7:0248L, 2000.
We investigated the effects of the nitric oxide (NO) donor molsidomine and the nitric
oxide synthase inhibitor N-nitro-l-arginine methyl ester (l-NAME) on pulmonary
endothelin (ET)-1 gene expression and ET-1 plasma levels in chronic hypoxic rats. Two
and four weeks of hypoxia (10% O2) significantly increased right ventricular systolic
pressure, the medial cross-sectional vascular wall area of the pulmonary arteries, and
pulmonary ET-1 mRNA expression (2-fold and 3.2-fold, respectively). ET-1 plasma
levels were elevated after 4 wk of hypoxia. In rats exposed to 4 wk of hypoxia,
molsidomine (15 mg•kg«minus»1•day«minus»1) given either from the beginning or after
2 wk of hypoxia significantly reduced pulmonary hypertension, pulmonary vascular
remodeling, pulmonary ET-1 gene expression, and ET-1 plasma levels. l-NAME
administration (45 mg•kg«minus»1•day«minus»1) in rats subjected to 2 wk of hypoxia
did not modify these parameters. Our findings suggest that in chronic hypoxic rats,
exogenously administered NO acts in part by suppressing the formation of ET-1. In
contrast, inhibition of endogenous NO production exerts only minor effects on the
pulmonary circulation and pulmonary ET-1 synthesis in these animals.
Received 11 May 2000; accepted in final form 25 September 2000
APS Manuscript Number L153-0.
Article publication pending Am J Physiol Lung Cell Mol Physiol
ISSN 1080-4757 Copyright 2000 The American Physiological Society.
Published in APStracts on 7 November 2000