PRESYNAPTIC DEFICIT OF SYMPATHETIC-NERVES - A CAUSE FOR DISTURBED SCIATIC-NERVE BLOOD-FLOW RESPONSIVENESS IN DIABETIC RATS

Reduced nerve blood flow is thought to play an important role in the p athogenesis of diabetic neuropathy. This disturbance in nerve blood fl ow might be the consequence of either microangiopathy or an impaired a utonomic innervation of the vasa nervorum. In order to differentiate b etween a vascular or an adrenergic-autonomic defect as the underlying cause of the disturbed nerve blood flow, we investigated the effects o f the adrenocorticotropic hormone [ACTH]-(4-9) analogue Org 2766 on sc iatic nerve blood flow under basal and adrenergic-stimulated condition s. Org 2766 has neuroprotective effects without cardiovascular effects . Treatment with Org 2766 was started 6 weeks after the induction of e xperimental diabetes mellitus. At week 12 the sciatic nerve blood flow , measured by laser-Doppler flowmetry, was reduced to 60% of the non-d iabetic level; blood pressure was unchanged in diabetic rats compared to non-diabetic rats. Basal haemodynamic values were not affected by O rg 2766 treatment. Vasa nervorum adrenergic responsiveness to tyramine (presynaptic) and phenylephrine (postsynaptic) was investigated. Diab etic rats showed adrenergic hyporesponsiveness. Treatment with Org 276 6 restored the reduced presynaptic response to tyramine without affect ing the reduced postsynaptic response to phenylephrine. It is conclude d that a presynaptic-sympathetic deficit of nervi vasorum causes a dis turbed flow responsiveness in diabetic rat sciatic nerve and that adre nergic autonomic disturbances in the vasa nervorum have only a small r ole in the reduced basal nerve blood flow of diabetic rats.