Sympathetic denervation caused by long-term noradrenaline infusions; prevention by desipramine and superoxide dismutase.
1. The effects of continuous intravenous infusion of noradrenaline (0.01 and 0.1 microgram kg-1 h-1) were studied in both the infused lateral saphenous vein and the contralateral saphenous vein of normal dogs. Noradrenaline, saline, noradrenaline + desipramine or noradrenaline + superoxide dismutase were infused using Alzet osmotic minipumps. 2. After a 5 day infusion period, the noradrenaline content in plasma and in both saphenous veins was determined, and the venous tissues submitted to light microscope morphometry and ultrastructural study and used for the determination of their O-methylation capacity (with [3H]-isoprenaline as a substrate). 3. Noradrenaline caused dose-dependent damage to the sympathetic nerve endings of the lateral saphenous veins. Concomitant changes in extraneuronal structure and function were observed (hypertrophy of smooth muscle cells, nuclear dysmorphy, thickening of the vessel wall, impairment in O-methylation capacity). 4. Desipramine and superoxide dismutase prevented or reduced the effects of noradrenaline on both the morphological and the biochemical parameters; the protection afforded by superoxide dismutase was more marked than that by desipramine. 5. It is concluded that moderately high doses of noradrenaline exert a 6-hydroxydopamine-like effect and that this chemical sympathectomy is partially or totally prevented by desipramine or superoxide dismutase. The data suggest that a substance derived from noradrenaline, in the formation of which free oxygen radicals are involved and which is subject to neuronal uptake, is the chemical entity responsible for the neurotoxic effect observed.
Albino Teixeira
A
A
Laboratório de Farmacologia, Faculdade de Medicina, Porto, Portugal.
Azevedo
I
I
Branco
D
D
Rodrigues-Pereira
E
E
Osswald
W
W
D000818:Animals; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology*; D004285:Dogs; D005347:Fibroblasts / Q000187:drug effects; D008297:Male; D008745:Methylation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D013482:Superoxide Dismutase; D003891:Desipramine; D009638:Norepinephrine