L-arginine-dependent nitric oxide synthase: a new metabolic pathway in the lung and airways

An L-arginine-dependent pathway, metabolising L-arginine to citrulline and nitrogen oxides, has been described in many cell types in different species, including man. Two subtypes of this nitric oxide synthase have been reported: a constitutive enzyme type, releasing nitric oxide after stimulation, is typically found in endothelial and neural cells; another subtype can be induced in macrophages after cytokine treatment. This review summarizes the literature on the known and proposed roles of this L-arginine-dependent nitric oxide production in different pulmonary processes. Nitric oxide has been reported to act as a neurotransmitter in the inhibitory nonadrenergic, noncholinergic nerves in the airways of guinea-pig and man. It is released in cytostatic processes by immune-stimulated alveolar macrophages. Recent data on the role of L-arginine-dependent processes in immune-complex-mediated lung injury, histamine-induced activation of guanylate cyclase or cytokine networks in the lung are also discussed. Finally, similarities and differences between tracheal epithelium-derived relaxing factor and nitric oxide are analysed. The details of the role and distribution of nitric oxide synthase in the (human) lung and airways are not yet completely understood. Nitric oxide is believed to play a role in various pulmonary physiological processes, such as bronchodilation and the cytotoxic action of certain cells. The modulation of nitric oxide release will therefore, most probably lead to application of novel therapies in diseases such as asthma and inflammatory pulmonary diseases.