K+ channel openers and suppression of airway hyperreactivity

Openers of ATP-sensitive K+ channels (K(ATP) channels) can reduce obstruction to airflow by suppressing hyperreactivity of intact airways. This property can be observed in hyperreactive animals with doses that are insufficient to relax airway smooth muscle in situ in normal animals. Hence, the potency of openers of K(ATP) channels as inhibitors of bronchospasm is greater in hyperreactive than in normal animals. A closely analogous property has been described in clinical and laboratory studies of established anti-asthma drugs. Such findings raise the possibility that the therapeutic benefit of these drugs may depend upon an opening of K+ channels, either directly or indirectly. In this review, John Morley suggests that compounds that open K+ channels and impair expression of airway hyperreactivity in the absence of direct smooth muscle spasmolysis will provide a novel approach to symptomatic therapy in asthma.