Structural and functional alterations caused at the extraneuronal level by sympathetic denervation of blood vessels

Abstract

The lateral saphenous vein of the dog and the rabbit ear artery were surgically denervated, by clamping the vessel or by removal of the superior cervical ganglion, respectively. Both procedures resulted in denervation of the vessels. The denervated, lateral saphenous vein was supersensitive to exogenous noradrenaline and inactivation of the amine (in oil immersion experiments) was slower in denervated vein strips than in control strips treated with cocaine. Incubation experiments with 3H-noradrenaline confirmed that denervated strips formed considerably fewer metabolites than control ones (in the absence or presence of cocaine) and that O-methylation of noradrenaline was reduced by about 50%. When the strips were incubated with 3H-isoprenaline, the denervated ones accumulated and metabolized isoprenaline to a lesser degree than control strips. Hydrocortisone did not reduce the accumulation of isoprenaline in the denervated vein and had only minor effects on O-methylation. The metabolism of noradrenaline and isoprenaline gradually recovered with time. In the ear artery, denervation was accompanied by a marked reduction in O-methylation, but not in accumulation, of isoprenaline. In both vessels there was a highly significant positive correlation between noradrenaline content and O-methylating capacity; in the saphenous vein accumulation of isoprenaline was also positively correlated to noradrenaline content. Morphological changes observed in the denervated vessels consisted essentially in dedifferentiation of smooth muscle cells (which attained larger dimensions, had an indented, large nucleus, augmented euchromatin and an increased amount of ribosomes), abundance of extracellular material and fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic denervation caused by long‐term noradrenaline infusions; prevention by desipramine and superoxide dismutase

“…These are characterized by degeneration of sympathetic nerve varicosities and extraneuronal changes of the same type as those previously described to occur after surgical denervation of these vessels (Branco et al, 1984). Thus, noradrenaline is shown to exert 6-hydroxydopaminelike effects.…”

“…We have found that denervation of the lateral saphenous vein of the dog induces marked morphological changes at the extraneuronal level, as well as an impairment of extraneuronal uptake and metabolism of noradrenaline and isoprenaline (Branco et al, 1984). The same work provided evidence for the inability of infused noradrenaline to prevent the described denervation-induced changes; it was observed that noradrenaline infusion appeared instead to aggravate the effects of denervation.…”

“…However, the fact remains that relatively low doses of noradrenaline have the potential to cause chemical sympathectomy and alterations at the extraneuronal level identical to those previously described to be induced by surgical or chemical denervation (Branco et al, 1984;Azevedo & Osswald, 1986;Dimitriadou et al, 1988). Furthermore, a clear-cut correlation between the amount of noradrenaline offered to the tissue and the degree of impairment of neuronal and extraneuronal structures was evident: first, because the chemical sympathectomy was evident only in the animals infused with the higher dose of noradrenaline; second, because for each dose the effects were consistently more marked on the vein where the infusion was effected (and therefore the plasma levels were substantially higher) than in the contralateral vein (where the plasma levels were lower, due to dilution and disposition of noradrenaline in the rest of the body).…”

“…The amounts of noradrenaline, SOD or desipramine were calculated so as to ensure infusion rates of 0.01 or 0.1pgkg-1h-' for noradrenaline, 5 The blood samples and fragments of the veins were used for determination of noradrenaline by high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.d. ), as described earlier (Branco et al, 1984). The remaining venous tissue was used for morphological studies, using the methods previously described (Azevedo et al, 1981;Branco et al, 1984;Sarmento et al, 1987) O-methylisoprenaline were separated by column chromatography, as described earlier in detail (Azevedo & Osswald, 1976).…”

“…), as described earlier (Branco et al, 1984). The remaining venous tissue was used for morphological studies, using the methods previously described (Azevedo et al, 1981;Branco et al, 1984;Sarmento et al, 1987) O-methylisoprenaline were separated by column chromatography, as described earlier in detail (Azevedo & Osswald, 1976).…”