Release and disposition of 3H-noradrenaline in the saphenous vein of neonate and adult dogs.
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 mumol/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 mumol/l cocaine (to inhibit uptake1), 41 mumol/l hydrocortisone (to reduce uptake2) and 50 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Moura
D
D
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Vaz-da-Silva
M J
MJ
Azevedo
I
I
Brandão
F
F
Guimarães
S
S
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism* / Q000493:pharmacokinetics; D010293:Pargyline / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology; D012501:Saphenous Vein / Q000254:growth & development / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
D011427:Propiophenones; D014316:Tritium; C006104:U 0521; D010293:Pargyline; D006854:Hydrocortisone; D009638:Norepinephrine