Nitric oxide metabolism in asthma pathophysiology

BackgroundAsthma, a chronic inflammatory disease is typically characterized by bronchoconstriction and airway hyper-reactivity.Scope of reviewA wealth of studies applying chemistry, molecular and cell biology to animal model systems and human asthma over the last decade has revealed that asthma is associated with increased synthesis of the gaseous molecule nitric oxide (NO).Major conclusionThe high NO levels in the oxidative environment of the asthmatic airway lead to greater formation of reactive nitrogen species (RNS) and subsequent oxidation and nitration of proteins, which adversely affect protein functions that are biologically relevant to chronic inflammation. In contrast to the high levels of NO and nitrated products, there are lower levels of beneficial S-nitrosothiols (RSNO), which mediate bronchodilation, due to greater enzymatic catabolism of RSNO in the asthmatic airways.General SignificanceThis review discusses the rapidly accruing data linking metabolic products of NO as critical determinants in the chronic inflammation and airway reactivity of asthma. This article is part of a Special Issue entitled Biochemistry of Asthma.

► Asthma is an inflammatory disease characterized by altered NO metabolism.
► Greater NO synthesis in asthma is accompanied by more nitration and less nitrosylation of airway-proteins.
► Greater protein nitration is associated with adverse effects on protein functions.
► Loss of S-nitrosothiol (SNO) products leads to loss of bronchodilator effects.
► Abnormal NO metabolism contributes to defining features of asthma.