A Prostacyclin Analogue, OP-41483α-CD, Restores the Ability of a β₂-Adrenergic Agonist to Stimulate Alveolar Fluid Clearance in Rats

Purpose.

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 β₂-adrenergic agonist, failed to increase alveolar fluid clearance. Therefore, we examined the effects of OP-41483α-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 cmH₂O. 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-41483α-CD restored the ability of 10⁻³ M terbutaline to stimulate alveolar fluid clearance. The effect of OP-41483α-CD was consistent with the effect of atenolol, a β₁-adrenergic antagonist. The effect of OP-41483α-CD on alveolar fluid clearance was unchanged in lungs inflated with nitrogen. Prostaglandin E (PGE)₁ and PGE₂ analogues had similar effects to OP-41483α-CD on alveolar fluid clearance.

Conclusion.

These results indicate that a prostacyclin analogue restores the ability of high-dose terbutaline to stimulate alveolar fluid clearance.