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CARDIOVASCULAR
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Volume 5, 2000, No 1 |
A
Study on Nitric Oxide Synthase mRNA Expression and Localization in
Intrapulmonary Arteries of Normobaric Hypoxic Rats
D. Junbao, Z. Min, Z. Bin, J. Jianfeng, L. Wanzhen, Z. Heping
Background: Hypoxic pulmonary hypertension has long been an important issue in vascular diseases. With regard to its pathologic and pathophysiologic changes, distal pulmonary arteries are mainly and predominantly impaired. However, the mechanisms responsible for the development of pulmonary hypertension, especially the mechanism responsible for its pulmonary vascular structural pathologic changes have not been clear. Endothelium-derived relaxing factor (EDRF) which was identified as nitric oxide (NO) played an important part in the regulatory mechanism of hypoxic pulmonary circulatory regulation. Since NO synthase (NOS) is responsible for synthesis speed of NO, it is necessary to do further studies on NOS gene expression and localization in different segments of pulmonary arteries under hypoxia vs. normoxia.
Methods: Twenty-one Wistar rats were randomly assigned into one-week hypoxia group (6 rats), two-week hypoxia group (8 rats) and control group (7 rats). Normobaric hypoxic challenge was done using a normobaric hypoxic chamber (CAMS, P. R. China) with an oxygen concentration of 10% ± 0.5%. Lung sections were obtained at the termination of the experiment. We studied constitutional NOS (cNOS) gene expression by endothelial cells and smooth muscle cells in different segments of pulmonary arteries by using in situ hybridization with a digoxigenin-labelled cNOS cRNA probe.
Results: In control rats, the positive integral scores of cNOS mRNA expression by endothelial cells of pulmonary arteries at level of bronchioles were higher than those in pulmonary arteries at levels of terminal bronchioles and respiratory bronchioles (q=8.13, 5.49, both p < 0.01). In one-week hypoxia group, cNOS mRNA expressions by endothelial cells of pulmonary arteries at levels of terminal bronchioles and bronchioles decreased obviously than those in control group (q=3.05, 8.70, p < 0.05, 0.01). While, cNOS mRNA expressions by smooth muscle cells of pulmonary arteries at levels of respiratory bronchioles and terminal bronchioles were obviously weak compared with those of control rats (q=4.04, 4.99, p < 0.05, 0.01). After two weeks of hypoxia, the strength of cNOS mRNA expressions by smooth muscle cells of pulmonary arteries at levels of respiratory bronchioles and terminal bronchioles decreased markedly as compared with those of control rats.
Conclusion: Our study showed that under normoxic condition, cNOS mRNA expression by endothelial cells was different in its strength amongst different segments of pulmonary arteries in normoxic rats. cNOS mRNA expressed most significantly in intrapulmonary arteries at level of bronchioles, proximal pulmonary arteries. Whereas under normobaric hypoxia, cNOS mRNA expression was inhibited in smooth muscle cells of more distal pulmonary arteries, which might provide molecular biologic implications for the fact that significant pulmonary pathologic and pathophysiologic changes were in distal other than proximal pulmonary arteries.
Key words: anoxia, nitric oxide, nitric oxide synthase, pulmonary artery
Address for Correspondence:
Prof. Du Junbao
Department of Pediatrics
First Hospital of Beijing Medical University
Beijing 100034
P. R. China
E-mail: junbaodu@ht.rol.cn.net
Reference:
(CVE. 2000; 5 (1): 53-56)
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