title: Estradiol decreases the acetylcholine-elicited airway reactivity in ovariectomized rats through an increase in epithelial acetylcholinesterase activity.
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 17beta-estradiol (E(2), 10 microg/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 (EC(200)RL) 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 (EC(200)RL, 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, E(2) treatment significantly increased the EC(50) of ACh (p = 0.01) but did not alter the CCRC to carbachol. Removing the epithelium or treatment with physostigmine abolished the difference in EC(50) of ACh between the groups. Acetylcholinesterase (AChE) activity of homogenized whole trachea was 1.4-fold greater in the E(2)-treated group compared with placebo (p = 0.02), whereas no difference was found in homogenized epithelium-free trachea. We conclude that E(2) treatment decreases airway responsiveness to ACh in ovariectomized rats at least in part by increasing AChE activity dependent on the presence of the epithelium.
authors.affiliation: INSERM U326, Service d'Exploration Fonctionelle Respiratoire, CHU Rangueil, Toulouse, France. degano.b@chu-toulouse.fr
authors.forename: B
authors.initials: B
authors.lastname: Degano
authors.forename: M C
authors.initials: MC
authors.lastname: Prévost
authors.forename: P
authors.initials: P
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Molimard
authors.forename: S
authors.initials: S
authors.lastname: Pontier
authors.forename: J
authors.initials: J
authors.lastname: Rami
authors.forename: R
authors.initials: R
authors.lastname: Escamilla
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000187:drug effects* / Q000502:physiology*; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000187:drug effects*; D012132:Respiratory Muscles / Q000187:drug effects / Q000503:physiopathology; D012720:Severity of Illness Index; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D004958:Estradiol; D000110:Acetylcholinesterase; D000109:Acetylcholine