Selective iNOS inhibitors

Our understanding of the role of nitric oxide (NO) produced by the inducibl e form of nitric oxide synthase (iNOS) in the pathophysiology of pulmonary diseases, including asthma, is at an early stage. At low levels, NO acts as a bronchodilator and a stimulator of ciliary activity. However, recent evi dence suggests that the sustained production of high levels of NO generated by iNOS results in the disruption of the airway epithelium, diminished cil iary function, a shift in the balance from a Th1- to a Th2-dominated respon se, and in addition, that it is a chemoattractant for eosinophils. For thes e reasons, it is likely that the selective inhibition of iNOS in asthma wil l result in decreased pulmonary inflammation and improved airway function. To date, no clinical study testing the efficacy of a selective iNOS inhibit or in asthma has been performed, but increasing evidence in various animal models of asthma with either selective iNOS inhibitors or iNOS gene disrupt ion supports this concept.