A prostacyclin analogue, OP-41483alpha-CD, restores the ability of a beta2-adrenergic agonist to stimulate alveolar fluid clearance in rats.
OBJECTIVE
It is not yet known whether a prostacyclin analogue can affect alveolar fluid clearance. According to recent studies, high-dose (10(-3) M) terbutaline, a beta(2)-adrenergic agonist, failed to increase alveolar fluid clearance. Therefore, we examined the effects of OP-41483alpha-CD, a prostacyclin analogue, on alveolar fluid clearance in the presence of high-dose terbutaline in rats.


METHODS
Albumin solution containing Evans blue dye and various drugs was instilled into the alveolar airspaces of isolated rat lungs, which were then inflated with 100% oxygen at an airway pressure of 8 cmH(2)O. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1 h.


RESULTS
Although 10(-5) and 10(-4) M terbutaline increased alveolar fluid clearance, 10(-3) M terbutaline did not. OP-41483alpha-CD restored the ability of 10(-3) M terbutaline to stimulate alveolar fluid clearance. The effect of OP-41483alpha-CD was consistent with the effect of atenolol, a beta(1)-adrenergic antagonist. The effect of OP-41483alpha-CD on alveolar fluid clearance was unchanged in lungs inflated with nitrogen. Prostaglandin E (PGE)(1) and PGE(2) analogues had similar effects to OP-41483alpha-CD on alveolar fluid clearance.


CONCLUSIONS
These results indicate that a prostacyclin analogue restores the ability of high-dose terbutaline to stimulate alveolar fluid clearance.
Sakuma
Tsutomu
T
Department of Thoracic Surgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
Zhao
Yabin
Y
Sugita
Makoto
M
Sagawa
Motoyasu
M
Hida
Mieko
M
Toga
Hirohisa
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism; D011654:Pulmonary Edema / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013726:Terbutaline / Q000494:pharmacology; D047391:alpha-Cyclodextrins
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; C051518:OP 41483-alpha-cyclodextrin; D001262:Atenolol; D011464:Epoprostenol; D013726:Terbutaline