Attenuation of nitric oxide synthase gene expression in rat lung induced by hypoxia

Abstract

In order to investigate the role of nitric oxide (NO) in pathogenesis of hypoxic pulmonary hypertension (HPH), the mean pulmonary arterial pressure (mPAP), mRNA expression of NO synthase (NOS) in lung tissues, cGMP levels, and their relationships were studied in rats exposed to hypoxia from 8 h to 28 days. The results showed that mPAP began to increase in animals exposed to 10 % O₂ for 8 h. Moreover, the longer the exposure, the higher the mPAP. Northern blot analysis and dot blot hybridization indicated that mRNA expression of NO in lung tissues of hypoxic rats tended to decrease with exposure days, but that of β-actin which acted as a control did not alter. The cGMP levels of plasma and lung tissues in hypoxic rats also inclined to be lower with exposure days. A marked negative correlations between the changes of cGMP levels and those of mPAP were found. It was suggested that mRNA expression of NOS gene was attenuated in hypoxic lung tissues, which may be one of important pathogenetic mechanisms of HPH.

Keywords

anoxia / lung / gene expression / nitric oxide synthase / rat

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