Release and disposition of ³H-noradrenaline in the saphenous vein of neonate and adult dogs

Summary

Release of ³H-noradrenaline and formation of ³H-metabolites were studied in the saphenous vein of newborn (mean age, 18 h) and adult dogs. Vein strips were incubated with 0.23 μmol/l of ³H-noradrenaline during 1 h and washed out for 110 min; thereafter, the perifusion fluid was collected in 5-min samples. Electrical stimulation was applied at 120 min (1 Hz, 2 ms, 100 V, for 5 min). In some experiments the tissues were preincubated with 1 mmol/l pargyline (to inhibit monoamine oxidase). In these experiments, 12 μmol/l cocaine (to inhibit uptake₁), 41 μmol/l hydrocortisone (to reduce uptake₂) and 50 μmol/l U-0521 (to inhibit COMT) were present during the perifusion. ³H-noradrenaline, ³H-DOPEG, ³H-NMN, ³H-DOMA and ³H-OMDA were separated by column chromatography. The noradrenaline content of the tissue was estimated by HPLC followed by electrochemical detection. A morphological study was also carried out by light and electron microscopy.

The endogenous noradrenaline content of the saphenous vein was 4.3 times higher in adults than in neonates. The number of varicosities was similar in adults and newborns but the number of vesicles per varicosity profile was 5 times higher in adults. Hence, the endogenous noradrenaline content per vesicle was about the same in adults and newborns. The accumulation of ³H-noradrenaline per vesicle was about 5 times higher in newborns than in adults. On the other hand, the vein wall media of neonates was about 3 times thinner than that of adults. The evoked fractional release of tritium was about 10 times higher in neonates than in adults, whether the inactivation pathways were blocked or not. This difference in the evoked fractional release therefore cannot be ascribed to any difference in the efficacy of the inactivation pathways between neonates and adults. On the other hand, the difference also cannot be ascribed to a different alpha₂-adrenoceptor-mediated inhibition of ³H-noradrenaline release since, as previously shown, this mechanism is as effective in newborns as in adults.

It is concluded that the evoked fractional release of ³H-noradrenaline is higher in neonates than in adults because in neonates the majority of varicosities (and vesicles) is situated closer to the surface of the tissue such that both uptake from the surrounding media into the stores and release from the stores into the surrounding media become easier in the neonates.