Description:
<jats:sec><jats:label /><jats:p>Enhanced airway reflex reactivity (EARR) and increased lung reactive oxygen species (ROS) are two features of asthma. A deterioration of asthma symptoms is associated with a declining estrogen level in females with unknown mechanisms. Sensitization of lung vagal C‐fiber afferents (LVCFAs) has been implicated in the pathogenesis of asthma. We investigated the influence of estrogen on the LVCFA‐mediated EARR induced by increased lung ROS in anesthetized female rats. Apneic response to intravenous capsaicin, a selective stimulant of LVCFAs, before and after spontaneous inhalation of aerosolized H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> (a major type of ROS; 0.05 % for 90 s) was measured as an index of airway reflex reactivity. We found that H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> inhalation induced a LVCFA‐mediated EARR in intact rats and this EARR was more prominent during the metestrus/diestrus (low estrogen) phase than during the proestrus (high estrogen) phase. In ovariectomized rats, subcutaneous 17β‐estradiol replacement, at a dose that mimics its level during the proestrus surge, suppressed the H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>‐induced EARR. The suppressive effect of 17β‐estradiol was reversed by pretreatment with ICI 182,780, an estrogen antagonist. These results suggest that endogenous and exogenous estrogen may alleviate ROS‐induced EARR in female rats possibly via suppression of sensitization of LVCFAs (NSC 98‐2320‐B‐010‐016‐MY3 and 98‐2628‐B‐040‐011‐MY3).</jats:p></jats:sec>