Purine agonists prevent trophic changes caused by sympathetic denervation

Abstract

Surgical denervation of the lateral saphenous vein of the dog causes marked extraneuronal changes, both of a morphological and functional type. In an attempt to investigate the factor(s) responsible for the trophic effects exerted by the sympathetic innervation on the dog saphenous vein we studied the effects of noradrenaline, adenosine, inosine and N-ethylcarboxamidoadenosine (NECA) on vascular tissue after sympathetic denervation. The saphenous vein was denervated using either surgical or chemical (6-hydroxydopamine, 6-OHDA) methods. Noradrenaline (0.1 μg/kg per h), adenosine (10 μg/kg per h), inosine (10 μg/kg per h) or NECA (0.1 μg/kg per h) were delivered continuously for 5 days through Alzet minipumps connected to the vein. 6-OHDA-induced denervation resulted in morphological changes similar to those described for surgical denervation. Smooth muscle cells and fibroblasts showed ultrastructural signs of increased synthetic activity and their size was significantly increased. In confirmation of earlier studies, constant i.v. infusions of noradrenaline did not prevent the morphological changes induced by denervation. Adenosine prevented the morphological changes induced by chemical or surgical denervation. Similarly to adenosine, infused NECA prevented the structural consequences of denervation. In contrast, inosine did not prevent the changes caused by surgical denervation. The results are compatible with an involvement of purines in the trophic effects of sympathetic innervation. Moreover, the effects of adenosine do not appear to be mediated by inosine.