Effects of ET-A receptor blockade on eNOS gene expression in chronic hypoxic rat lungs

Blumberg, Friedrich C. and Wolf, Konrad and Arzt, Michael and Lorenz, Cornelia and Riegger, Guenter A. J. and Pfeifer, Michael (2003) Effects of ET-A receptor blockade on eNOS gene expression in chronic hypoxic rat lungs. JOURNAL OF APPLIED PHYSIOLOGY, 94 (2). pp. 446-452. ISSN 8750-7587

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Abstract

We tested the hypothesis that pulmonary endothelial nitric oxide synthase (eNOS) gene expression is primarily regulated by hemodynamic factors and is thus increased in rats with chronic hypoxic pulmonary hypertension. Furthermore, we examined the role of endothelin (ET)-1 in this regulatory process, since ET-1 is able to induce eNOS via activation of the ET-B receptor. Therefore, chronic hypoxic rats (10% O-2) were treated with the selective ET-A receptor antagonist LU-135252 (50 mg.kg(-1).day(-1)). Right ventricular systolic pressure and cross-sectional medial vascular wall area of pulmonary arteries rose significantly, and eNOS mRNA levels increased 1.8- and 2.6-fold after 2 and 4 wk of hypoxia, respectively (each P < 0.05). Pulmonary ET-1 mRNA and ET-1 plasma levels increased significantly after 4 wk of hypoxia (each P < 0.05). LU-135252 reduced right ventricular systolic pressure, vascular remodeling, and eNOS gene expression in chronic hypoxic rats (each P < 0.05), whereas ET-1 production was not altered. We conclude that eNOS expression in chronic hypoxic rat lungs is modified predominantly by hemodynamic factors, whereas the ET-B receptor-mediated pathway and hypoxia seem to be less important.

Item Type: Article
Uncontrolled Keywords: NITRIC-OXIDE SYNTHASE; INDUCED PULMONARY-HYPERTENSION; INDUCED UP-REGULATION; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; PROLIFERATION; PROSTACYCLIN; CIRCULATION; DEFICIENCY; ANTAGONIST; pulmonary hypertension; endothelin; hypoxia; endothelial nitric oxide synthase
Subjects: 500 Science > 570 Life sciences
600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin II
Biology, Preclinical Medicine > Institut für Physiologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 20 Sep 2021 09:47
Last Modified: 20 Sep 2021 09:47
URI: https://pred.uni-regensburg.de/id/eprint/39310

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