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1 Department of Internal Medicine II and 2 Institute of Physiology, University of Regensburg, 93042 Regensburg, Germany
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
1 · day
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
1 · day
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.
pulmonary hypertension; chronic hypoxia; nitric oxide
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