Laboratory investigation; a journal of technical methods and pathology
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To examine the effects of cigarette smoke on nitric oxide synthase (NOS) gene expression and protein production, groups of rats were exposed to smoke once only or daily and were sacrificed after 1, 2, 7, or 28 days of exposure. NOS-1, NOS-2, and NOS-3 mRNAs in whole lung were quantified using reverse transcription polymerase chain reaction (RT-PCR), and NOS protein levels were determined by Western blots. Neither NOS-1 gene expression nor protein levels changed with smoke exposure. ⋯ Protein distribution, as determined by immunohistochemical staining, was identical to mRNA tissue distribution, and these distributions were not changed by smoke. We conclude that smoke exposure induces a rapid but transient increase in transcription of NOS-2, and a sustained increase in transcription and translation of NOS-3; up-regulation of NOS occurs within the anatomic compartment where these genes are normally expressed. These findings indicate that cigarette smoke can directly and rapidly affect NOS expression, and thus potentially affect the function of the pulmonary vasculature.