The inactivation of noradrenaline and isoprenaline in dogs.

1. The removal of infused noradrenaline and isoprenaline from the circulation of the dog has been studied, using the blood-bathed organ technique.2. Both catecholamines were removed in peripheral vascular beds; in all organs studied, noradrenaline was removed to a greater degree than isoprenaline.3. The hind legs removed an average of 60% of the noradrenaline passing through, but only 34% of the isoprenaline. With noradrenaline, the degree of removal decreased as the concentration increased, but with isoprenaline, the degree of removal increased with concentration.4. After phenoxybenzamine, the proportion of isoprenaline removed was unchanged, whereas that of noradrenaline was decreased. The change in removal with the concentration of noradrenaline was also abolished.5. The results are consistent with the concept that a small fraction of infused noradrenaline is removed from the circulation by Uptake(1) and that this is blocked by phenoxybenzamine. Isoprenaline, and the rest of the noradrenaline, are removed by another process (Uptake(2)?) followed by intracellular metabolism. This inactivation process is unaffected by phenoxybenzamine in concentrations sufficient to give alpha-adrenoceptor blockade.6. After isoprenaline infusions, a substance sometimes appeared in the circulation which contracted the blood-bathed organs.7. The systemic pressure response to vaso-active hormones is not a reliable indicator of the concentration of hormone in the arterial circulation.