Denopamine stimulates alveolar fluid clearance via cystic fibrosis transmembrane conductance regulator in rat lungs.
OBJECTIVE
The objective of this study was to test the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance.


METHODS
Isotonic 5% albumin solutions containing different pharmacological agents were instilled into the alveolar spaces of the isolated rat lungs. The lungs were inflated with 100% oxygen at an airway pressure of 7 cm H(2)O and placed in a humidified incubator at 37 degrees C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1 h. To test the hypothesis, we determined whether CFTR Cl(-) channel inhibitors (glibenclamide and CFTR(inh)-172) inhibited the effect of denopamine, a beta(1)-adrenergic agonist, on stimulation of alveolar fluid clearance in the isolated rat lungs.


RESULTS
Denopamine increased alveolar fluid clearance in a dose-dependent manner. Atenolol, a beta(1)-adrenergic antagonist, abolished the effects of denopamine on stimulation of alveolar fluid clearance. Although glibenclamide alone or CFTR(inh)-172 alone did not change basal alveolar fluid clearance, these CFTR inhibitors inhibited the effect of denopamine on alveolar fluid clearance.


CONCLUSIONS
CFTR plays a role in beta(1)-adrenergic agonist-stimulated alveolar fluid clearance in rat lungs.
Gu
Xiu
X
Thoracic Surgery, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
Wang
Zheng
Z
Xu
Jin
J
Maeda
Sumiko
S
Sugita
Makoto
M
Sagawa
Motoyasu
M
Toga
Hirohisa
H
Sakuma
Tsutomu
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C037293:denopamine