Differential effects of low and high-dose estradiol on airway reactivity in ovariectomized rats.
The aim of this animal study was to test the hypothesis that low and high doses of 17beta-estradiol (E2) may differentially influence airway responsiveness. Ovariectomized female rats received either placebo or E2 (10 or 100 microg/kg per day) for 21 days. The concentration of inhaled acetylcholine (ACh) required to double pulmonary resistance (EC200 RL) was calculated as the in vivo index of airway responsiveness. Ex vivo airway responsiveness was evaluated by the cumulative concentration-response curve (CCRC) of isolated tracheal segments. Rats treated with low-dose E2 were less responsive to ACh than rats given either placebo or high-dose E2 (P=0.003). Ex vivo, low-dose E2 treatment decreased (P=0.01) and high-dose E2 increased the potency of ACh (P<0.001) compared to placebo. E2 treatment did not alter smooth muscle cross-sectional area or epithelium thickness. Accumulation of liquid within the tracheal mucosa was moderately enhanced by high-dose E2 treatment compared with animals given either placebo or low-dose E2 (P=0.03). We conclude that E2 treatment has differential, dose-dependent effects on airway responsiveness to acetylcholine.
Degano
Bruno
B
Service de Pneumologie, CHU Purpan, TSA 40031, 31059 Toulouse, Cedex 9, France. degano.b@chu-toulouse.fr
Mourlanette
Pierre
P
Valmary
Séverine
S
Pontier
Sandrine
S
Prévost
Marie-Claude
MC
Escamilla
Roger
R
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005070:Evans Blue / Q000378:metabolism; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects; D008170:Lung Compliance / Q000187:drug effects; D009929:Organ Size; D010052:Ovariectomy; D051381:Rats; D012132:Respiratory Muscles / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000502:physiology; D014599:Uterus
D005070:Evans Blue; D004958:Estradiol; D000109:Acetylcholine