The inactivation of noradrenaline and isoprenaline in dogs

Abstract

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 Uptake₁ and that this is blocked by phenoxybenzamine. Isoprenaline, and the rest of the noradrenaline, are removed by another process (Uptake₂?) followed by intracellular metabolism. This inactivation process is unaffected by phenoxybenzamine in concentrations sufficient to give α-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.