Dobutamine increases alveolar liquid clearance in ventilated rats by beta-2 receptor stimulation.
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 microCi 125I-albumin. The concentrations of the labeled and unlabeled albumin were used to quantify alveolar liquid clearance. Dopamine, whether given intra-alveolar (10(-4) M) or intravenously (5-10 micrograms/kg/min), had no effect. However, both intra-alveolar (10(-4) M) and intravenous (5 micrograms/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 (10(-3) M), an inhibitor of sodium uptake. In summary, the beta-2 receptor mediates beta-adrenergic stimulation of alveolar epithelial sodium and fluid transport.
Tibayan
F A
FA
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Chesnutt
A N
AN
Folkesson
H G
HG
Eandi
J
J
Matthay
M A
MA
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000584:Amiloride / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004280:Dobutamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000502:physiology; D012121:Respiration, Artificial / Q000295:instrumentation / Q000379:methods; D013268:Stimulation, Chemical; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D004280:Dobutamine; D000584:Amiloride; D004298:Dopamine