Am. J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, 1849-1854

Estradiol Decreases the Acetylcholine-elicited Airway Reactivity in Ovariectomized Rats through an Increase in Epithelial Acetylcholinesterase Activity

BRUNO DEGANO, MARIE-CLAUDE PRÉVOST, PATRICK BERGER, MATHIEU MOLIMARD, SANDRINE PONTIER, JACQUES RAMI, and ROGER ESCAMILLA

INSERM U³ 26, Service d'Exploration Fonctionnelle Respiratoire and INSERM U397, Service de Pneumologie et d'Allergologie, CHU Toulouse; and Laboratoire de Physiologie Cellulaire Respiratoire, Département de Pharmacologie, EMI, Bordeaux, France

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 17-estradiol (E₂, 10 µg/kg per d for 21 d) given to oophorectomized female rats modifies airway responsiveness to cholinergic agonists, compared with oophorectomized rats given placebo. In vivo, the concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC₂₀₀RL) in anesthetized spontaneously breathing tracheotomized rats was calculated as an index of airway responsiveness. E₂-treated rats were less responsive to ACh than placebo-treated rats (EC₂₀₀RL, 9.40 ± 1.48 vs. 1.52 ± 0.85 mg · ml¹, respectively). Ex vivo airway responsiveness was evaluated with the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Compared with placebo, E₂ treatment significantly increased the EC₅₀ of ACh (p = 0.01) but did not alter the CCRC to carbachol. Removing the epithelium or treatment with physostigmine abolished the difference in EC₅₀ of ACh between the groups. Acetylcholinesterase (AChE) activity of homogenized whole trachea was 1.4-fold greater in the E₂-treated group compared with placebo (p = 0.02), whereas no difference was found in homogenized epithelium-free trachea. We conclude that E₂ treatment decreases airway responsiveness to ACh in ovariectomized rats at least in part by increasing AChE activity dependent on the presence of the epithelium.

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