DOPAMINE STIMULATES SODIUM-TRANSPORT AND LIQUID CLEARANCE IN RAT LUNGEPITHELIUM

Pulmonary edema clearance is driven primarily by active sodium transpo rt out of the alveoli, mediated predominantly by apical sodium channel s and the basolateral NA,K-ATPase. We postulated that dopamine, analog ous to its effects in other transporting epithelia, could regulate the se sodium transport mechanisms and affect lung liquid clearance. We th erefore studied the effects of dopamine on sodium transport and liquid clearance in isolated perfused rat lungs. Instillation of dopamine in to the airways caused a dose-dependent increase in liquid clearance fr om isolated rat lungs of up to 33% above control values at 10(-8) to 1 0(-4) M concentrations. 10(-6) M amiloride, which selectively inhibits apical sodium channels, decreased basal liquid clearance by 34% but d id not inhibit the dopamine-mediated stimulation of lung liquid cleara nce. Instillation of 10(-4) M amiloride into rat airways, which inhibi ts other sodium transport mechanisms non-selectively, decreased basal lung liquid clearance by 49% and inhibited the dopamine-mediated stimu lation of lung liquid clearance. Perfusion of rat lungs with 5 x 10(-4 ) M ouabain to specifically inhibit Na,K-ATPase reduced both basal cle arance (by 55%) and the dopamine-stimulated increase in lung fluid cle arance. Conceivably, the stimulation of lung liquid clearance by dopam ine is due to a modulation of Na,K-ATPase in the pulmonary epithelium.