Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium.
Pulmonary edema clearance is driven primarily by active sodium transport out of the alveoli, mediated predominantly by apical sodium channels and the basolateral NA,K-ATPase. We postulated that dopamine, analogous to its effects in other transporting epithelia, could regulate these sodium transport mechanisms and affect lung liquid clearance. We therefore studied the effects of dopamine on sodium transport and liquid clearance in isolated perfused rat lungs. Instillation of dopamine into the airways caused a dose-dependent increase in liquid clearance from isolated rat lungs of up to 33% above control values at 10(-8) to 10(-4) M concentrations. 10(-6) M amiloride, which selectively inhibits apical sodium channels, decreased basal liquid clearance by 34% but did not inhibit the dopamine-mediated stimulation of lung liquid clearance. Instillation of 10(-4) M amiloride into rat airways, which inhibits other sodium transport mechanisms non-selectively, decreased basal lung liquid clearance by 49% and inhibited the dopamine-mediated stimulation of lung liquid clearance. Perfusion of rat lungs with 5 x 10(-4) M ouabain to specifically inhibit Na,K-ATPase reduced both basal clearance (by 55%) and the dopamine-stimulated increase in lung fluid clearance. Conceivably, the stimulation of lung liquid clearance by dopamine is due to a modulation of Na,K-ATPase in the pulmonary epithelium.
Barnard
M L
ML
Columbia Michael Reese Hospital and Medical Center, Pulmonary Research Laboratory, Chicago, IL 60616, USA.
Olivera
W G
WG
Rutschman
D M
DM
Bertorello
A M
AM
Katz
A I
AI
Sznajder
J I
JI
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004848:Epithelium; D015633:Extravascular Lung Water / Q000187:drug effects*; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*
D015222:Sodium Channels; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine