Am. J. Respir. Crit. Care Med., Volume 156, Number 2, August 1997, 438-444

Dobutamine Increases Alveolar Liquid Clearance in Ventilated Rats by Beta-2 Receptor Stimulation

FRED A. TIBAYAN, ASHA N. CHESNUTT, HANS G. FOLKESSON, JON EANDI, and MICHAEL A. MATTHAY

Cardiovascular Research Institute, University of California, San Francisco

Although it is well known that beta-adrenergic agonist stimulation increases alveolar epithelial sodium and fluid transport, it is not known whether the beta-1 or the beta-2 receptor mediates this effect. Two clinically relevant beta-adrenergic agonists, dopamine (beta-1 agonist) and dobutamine (beta-1 and beta-2 agonist) were used to define the contribution of these two beta-receptors to beta-adrenergic stimulated fluid clearance from the air spaces of the lungs. Alveolar fluid clearance was measured in anesthetized, ventilated rats over one hour after instilling an isosmolar 5% albumin solution in Ringer's lactate with 3 µCi ¹²⁵I-albumin. The concentrations of the labeled and unlabeled albumin were used to quantify alveolar liquid clearance. Dopamine, whether given intra-alveolar (10⁴ M) or intravenously (5-10 µg/kg/min), had no effect. However, both intra-alveolar (10⁴ M) and intravenous (5 µg/kg/min) dobutamine increased alveolar liquid clearance by approximately 50% over one hour compared to controls. ICI 118,551, a potent and specific beta-2 antagonist, blocked the effect of dobutamine. The dobutamine effect was blocked by amiloride (10³ M), an inhibitor of sodium uptake. In summary, the beta-2 receptor mediates beta-adrenergic stimulation of alveolar epithelial sodium and fluid transport.

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