BRADYKININ-EVOKED SENSITIZATION OF AIRWAY SENSORY NERVES - A MECHANISM FOR ACE-INHIBITOR COUGH

Cough accompanied by an increased sensitivity of the cough reflex is t he most common symptom of inflammatory airway disease(1,5). This sympt om is also frequently reported in patients receiving angiotensin-conve rting converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension(2-4), although the underlying mechanism is unknown. We have investigated the possibility that the inflammatory peptide brady kinin, normally degraded by ACE, causes sensitization of airway sensor y nerves and an enhancement of the cough reflex in conscious guinea pi gs. Treatment of guinea pigs for two weeks with captopril led to an in creased cough response to inhaled citric acid, which was prevented by concomitant treatment with the bradykinin receptor antagonist icatiban t. A similar icatibant-sensitive enhancement of citric acid-evoked cou gh was seen in untreated animals after prior inhalation of bradykinin, although cough evoked by hypertonic saline was unaffected. In electro physiological studies performed in vitro, responses of single vagal C fibers to capsaicin, applied to receptive fields of single-fiber units in the trachea, were also markedly increased after perfusion with bra dykinin, whereas A delta fiber responses to hypertonic saline were una ffected. These results indicate that bradykinin-evoked sensitization o f airway sensory nerves may underlie the pathogenesis of ACE-inhibitor cough. Bradykinin receptor antagonists may be of benefit in treating chronic cough seen with this and other inflammatory conditions.