EFFECT OF AMINOGUANIDINE ON THE FREQUENCY OF NEUROAXONAL DYSTROPHY INTHE SUPERIOR MESENTERIC SYMPATHETIC AUTONOMIC GANGLIA OF RATS WITH STREPTOZOCIN-INDUCED DIABETES

Aminoguanidine, which prevents formation of advanced glycation end pro ducts and is a relatively selective potent inhibitor of the inducible (versus constitutive) isoform(s) of nitric oxide synthase, has been re ported to ameliorate structural and functional abnormalities in periph eral somatic nerves in rats with streptozocin (STZ)-induced diabetes. In the present studies, the effects of aminoguanidine treatment on ult rastructural changes in the autonomic nervous system of rats with STZ- induced diabetes were examined. The frequency of neuroaxonal dystrophy , the neuropathological hallmark of sympathetic autonomic neuropathy i n diabetic rats, increased 9- to 11-fold in the superior mesenteric ga nglia of 7- and 10-month STZ-diabetic rats compared with that in age-m atched controls. Administration of aminoguanidine continuously from th e time of induction of diabetes at a dose equal to or in excess of tha t providing a salutary effect in the diabetic somatic peripheral nervo us system did not alter the severity of diabetes as assessed by plasma glucose level, 24-h urine volume, and levels of glycated hemoglobin. Chronic aminoguanidine therapy did not diminish the frequency or affec t the ultrastructural appearance of neuroaxonal dystrophy in diabetic or age-matched control rat sympathetic ganglia after 7 or, 10 months o f continuous administration. Our findings (under these experimental co nditions) do not support a role for, aminoguanidine-sensitive processe s in the development of sympathetic neuroaxonal dystrophy in diabetic rats. Glycation-linked aminoguanidine-insensitive processes, however, such as the formation of early glucose adducts (Schiff bases and Amado ri products) with intracellular and/or extracellular proteins and amin e-containing lipids, superoxide anion generation during subsequent aut oxidation of these glucose adducts, and non-glycative processes, remai n potential pathogenetic mechanisms for diabetic autonomic neuropathy.