Effects of sympathetic denervation on liver fibroblasts: prevention by adenosine

Abstract

1. The effect of chemical denervation with 6-hydroxydopamine (6-OHDA) upon portal tract fibroblasts of dogs and rabbits was studied. 2. Denervation led to a significant increase in the density of portal tract fibroblasts both in the dog and in the rabbit. 3. Mast cells, present in the dog but not in the rabbit liver, were also significantly increased by denervation. 4. Noradrenaline depletion induced by reserpine did not increase the density of fibroblasts in the liver portal spaces of the dog. Mast cell density, however, was actually decreased when compared with control. 5. Continuous i.v. infusions of adenosine (10 micrograms kg-1h-1) to dogs totally prevented the effects of 6-OHDA-induced denervation upon fibroblast and mast cell densities in the portal space connective tissue. 6. It is concluded that the sympathetic nervous system is exerting a repressive effect on liver fibroblasts, as was found to occur in various other mammalian tissues. Mast cells, which are known to be activated in various pathological processes of fibrosis, appear to share with fibroblasts a modulating effect from the sympathetic nervous system. 7. The results strongly support the hypothesis of adenosine being the sympathetic trophic factor involved in the control of fibroblasts in the connective tissue of dog liver. A similar role for adenosine had previously been found in the dog saphenous vein.