Different desipramine-sensitive pulmonary removals of plasma epinephrine and norepinephrine in dogs

The lungs are an important site for the clearance of norepinephrine from the circulation, but the mechanism of removal and its importance for clearance of epinephrine require clarification. In the present study, 3H-labeled epinephrine and norepinephrine were infused intravenously into anesthetized dogs, and blood samples were taken from the pulmonary artery and aorta to compare pulmonary extractions of both catecholamines before and after administration of the neuronal uptake blocking drug, desipramine. Circulating [3H]norepinephrine and [3H]-epinephrine were both extracted by the lungs, but fractional extraction of [3H]epinephrine (8.1 +/- 1.1%) was half that of [3H]norepinephrine (16.9 +/- 1.9%). Pulmonary extractions of both catecholamines were completely blocked by desipramine. Desipramine-sensitive removal accounted for a tenth of the total body extraction of [3H]epinephrine and a third that of [3H]norepinephrine. Pulmonary removal of [3H]epinephrine was 14% that of the total body clearance, whereas pulmonary removal of [3H]norepinephrine was 25% that of the total body clearance. The study showed the following: removal of catecholamines by the canine lung in vivo is by desipramine-sensitive uptake; uptake is half as efficient for epinephrine as norepinephrine: and, pulmonary removal contributes importantly to the desipramine-sensitive component of total body catecholamine clearance.