COMPARISON OF NORADRENALINE AND ISOPRENALINE REMOVAL IN THE CANINE HINDLIMB AND KIDNEY

Abstract
1. Because isoprenaline is not a substrate for neuronal uptake (Uptake‐1, U‐1), the difference in regional removal of isoprenaline from regional removal of the sympathetic neurotransmitter noradrenaline has been proposed as an index of regional U‐1 activity. 2. U‐1 activity has not been assessed in the kidney, where decreased U‐1 may account for increased renal spillover of noradrenaline into plasma in disorders such as essential hypertension. 3. Tracer‐labelled noradrenaline and isoprenaline were simultaneously infused intravenously into anaesthetized dogs, and the regional removal of noradrenaline and isoprenaline was measured in the hindlimb and kidney after administration of the U‐1 blocker desipramine, hydrocortisone, which inhibits extra‐neuronal uptake of noradrenaline (Uptake‐2, U‐2), or no drug. 4. Hindlimb removal of noradrenaline (51%) exceeded that of isoprenaline (36%). Desipramine abolished this difference by decreasing removal of noradrenaline without affecting removal of isoprenaline. Renal removal of isoprenaline exceeded that of noradrenaline (74% vs 54%) even after U‐1 blockade. Hydrocortisone did not affect removal of noradrenaline or isoprenaline in either bed. 5. The results suggest that differences in removal of noradrenaline and isoprenaline reflect U‐1 activity in the hindlimb but not in the kidney; U‐1 is much more important than U‐2 in the regional removal of noradrenaline; and one mechanism of noradrenaline removal in the kidney is by neuronal uptake.

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