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L-Arginine Metabolism in the Lung: Reciprocal Regulation of the NOS and Arginase Pathways

It has been known for 20 years that the production of nitric oxide (NO) by the NO synthase (NOS) isozymes is important in the maintenance of airways tone. Over the past decade, however, it has become increasingly apparent that competition between the NOS and arginase pathways for L-arginine, limits NO production. Imbalances between these pathways have been implicated in the airways hyperresponsiveness (AHR) of asthma. Thus, a delicate balance between the NOS and arginase pathways is maintained through the intracellular synthesis of endogenous NOS and arginase inhibitors. More recently, the liberation of methylarginines has emerged as an additional modifier of L-arginine uptake and metabolism in the lung. In this review we discuss the reciprocal regulation of the NOS and arginase pathways and methylarginines and their roles in the airways hyperresponsiveness of asthma.