Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 164, Issue 10, Pages 1849-1854Publisher
AMER THORACIC SOC
DOI: 10.1164/ajrccm.164.10.2102009
Keywords
acetylcholinesterase; airway reactivity; estradiol; rat
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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 beta -estradiol (E-2, 10 mug/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. E-2-treated rats were less responsive to ACh than placebo-treated rats (EC200RL, 9.40 +/- 1.48 vs. 1.52 +/- 0.85 mg, ml(-1), 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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