Nitric oxide induces airway smooth muscle cell relaxation by decreasing the frequency of agonist-induced Ca oscillations

In the airways and lungs, nitric oxide (NO) is produced by epithelial ciliated cells, type II alveolar cells, and neural fibers that innervate the airway smooth muscle cells (SMCs) (Ricciardolo et al., 2004). It has been suggested that the NO released by these cells decreases airway resistance and that NO, released by neural fibers, is a major nonadrenergic, noncholinergic neurotransmitter responsible for airway SMC relaxation (Belvisi et al., 1995). In addition, airway inflammation is associated with a considerable increase in NO synthesis by inflammatory cells, including macrophages, mast cells, and neutrophils. However, in asthma, airway inflammation is accompanied by airway hyperresponsiveness, a behavior characterized by increased airway contraction in response to a variety of stimuli that suggests an impediment of the airways to relax in response to NO and other natural or pharmacological bronchodilators (Ricciardolo et al., 2004). The mechanisms responsible for these asthmaassociated changes are still not completely understood.