Comparison of noradrenaline and isoprenaline removal in the canine hindlimb and kidney.
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. 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. 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. 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. 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.
D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D006614:Hindlimb / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology; D007545:Isoproterenol / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*
D007545:Isoproterenol; D003891:Desipramine; D006854:Hydrocortisone; D009638:Norepinephrine