Constitutive expressions of type INOS in human airway smooth muscle cells:evidence for an antiproliferative role

In airway diseases, smooth muscle cells can proliferate at exaggerated rate s; thus, the identification of endogenous pathways that limit proliferative responses is important. Here we show that human airway smooth muscle expre ss type I nitric oxide synthase (NOS), which results in inhibition of DNA s ynthesis and cell proliferation. In addition, superoxide dismutase (SOD), a cell-permeable mimetic that increases the biological half-life and therefo re enhances the biological activity of endogenously released nitric oxide ( NO), or NO-releasing drugs also greatly reduce DNA synthesis and cell proli feration. Observations in this study have important clinical implications: 1) NOS inhibition may exacerbate airway disease and 2) inhaled SOD/mimetics or NO/nitrovasodilators may be therapies for the treatment of asthma or ch ronic obliterative pulmonary disease.