Structural changes and effect of denopamine on alveolar fluid clearance in hypoxic rat lungs

Abstract

Terbutaline (β₂-adrenergic agonist) can increase alveolar fluid clearance (AFC) under physiologic and pathologic conditions. It is unknown whether 1-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of denopamine (β₁- adrenergic agonist ) on AFC in hypoxic lung injury and the possible mechanisms involved. Hypoxic rats were exposed to 10% oxygen. 10^-5mol/L denopamine alone or combined with β receptor antagonists, Na⁺ channel blocker, or Na⁺/K⁺-ATPase blocker were perfused into the alveolar space of rats exposed to 10% oxygen for 48 h. AFC and total lung water content (TLW) were measured. AFC did not change for the first 24 h but then decreased after 48h exposure to 10% oxygen. The perfusion of denopamine significantly increased AFC in normoxic and hypoxic rats. The AFC- stimulating effect of denopamine lowered with amiloride (a Na⁺ channel blocker) and ouabain (a Na⁺/K⁺-ATPase inhibitor) by 35 and 53%, respectively. Colchicine significantly inhibited the effect of denopamine. Denopamine can increase the AFC during hypoxic lung injury in rats and accelerate the absorption of pulmonary edema.

Key words: 1-Adrenergic agonist, hypoxia, pulmonary edema, alveolar epithelium.