Role of estrogen on acetylcholine-elicited airway reactivity in ovariectomized rats: study of the possible involved mechanisms

ABSTRACT

Estrogen replacement therapy [ERT] is frequently prescribed for postmenopausal women. Epidemiological data suggest that sex hormones may play a role in the expression of asthma, but the mechanism[s] whereby this influence is mediated remain[s] unclear. To better understand the role of physiologic doses of estrogens in airway function, we tested the hypothesis that estradiol [E[2], 10 micro g/kg/d for 21 d] given to oophorectomized female rats modifies airway responsiveness to acetylcholine [Ach], compared with oophorectomized rats given placebo. In vitro airway responsiveness was evaluated with the cumulative concentration-response curve [CCRC] of isolated tracheal spirals. Compared with placebo, E[2] treatment significantly increased the EC[50] of Ach but did not alter the CCRC to either carbachol [CCh] or tracheal pre-treatment with physostigmine. In addition, L-arginine pre-incubation of tracheal spirals increased significantly the EC[50] of Ach in the placebo-treated group and this effect was more prominent with E[2]-treatment. L-NAME abolished the effect of L-arginine on the CCRC of the placebo treated spirals, however with E[2]-treatment, this effect was less prominent. We concluded that E[2] treatment decreased airway responsiveness to Ach in ovariectomized rats at least in part by increasing acetylcholine esterase [AChE] activity and by modifying the airway NO production