Purine agonists prevent trophic changes caused by sympathetic denervation

Area of Science:

• Vascular biology
• Neuropharmacology
• Cellular physiology

Background:

• Sympathetic innervation exerts trophic effects on vascular tissue.
• Denervation of the dog saphenous vein leads to significant extraneuronal morphological and functional changes.

Purpose of the Study:

• To investigate the factors responsible for the trophic effects of sympathetic innervation on the dog saphenous vein.
• To determine the role of noradrenaline, adenosine, inosine, and N-ethylcarboxamidoadenosine (NECA) in maintaining vascular tissue integrity after denervation.

Main Methods:

• Dog saphenous veins were denervated using surgical methods or chemical sympathectomy with 6-hydroxydopamine (6-OHDA).
• Continuous intravenous infusions of noradrenaline, adenosine, inosine, or NECA were administered for 5 days via Alzet minipumps.
• Morphological and ultrastructural changes in vascular smooth muscle cells and fibroblasts were assessed.

Main Results:

• 6-OHDA-induced denervation caused morphological changes, including increased size and synthetic activity of smooth muscle cells and fibroblasts.
• Continuous noradrenaline infusion did not prevent denervation-induced morphological changes.
• Adenosine and NECA infusions prevented the structural consequences of both surgical and chemical denervation.
• Inosine infusion did not prevent the changes observed after surgical denervation.

Conclusions:

• Purines, particularly adenosine and NECA, are implicated in the trophic effects of sympathetic innervation on vascular tissue.
• The protective effects of adenosine suggest its role in maintaining vascular integrity post-denervation.
• Adenosine's effects appear independent of inosine mediation.