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

Abstract

ABSTRACT In airway diseases, smooth muscle cells can proliferate at exaggerated rates; thus, the identification of endogenous pathways that limit proliferative responses is important. Here we show that human airway smooth muscle express type I nitric oxide synthase (NOS), which results in inhibition of DNA synthesis and cell proliferation. In addition, superoxide dismutase (SOD), a cell‐permeable mimetic that increases the biological half‐life and therefore enhances the biological activity of endogenously released nitric oxide (NO), or NO‐releasing drugs also greatly reduce DNA synthesis and cell proliferation. 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 chronic obliterative pulmonary disease.—Patel, H. J., Belvisi, M. G., Donnelly, L. E., Yacoub, M. H., Chung, K. F., Mitchell, J. A. Constitutive expressions of type I NOS in human airway smooth muscle cells: evidence for an antiproliferative role. FASEB J . 13, 1810–1816 (1999)