Effect of aminoguanidine on the frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic autonomic ganglia of rats with streptozocin-induced diabetes

Robert E. Schmidt, Denise A. Dorsey, Lucie N. Beaudet, Karen M. Reiser, Joseph R. Williamson, Ronald Tilton

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Aminoguanidine, which prevents formation of advanced glycation end products and is a relatively selective potent inhibitor of the inducible (versus constitutive) isoform(s) of nitric oxide synthase, has been reported to ameliorate structural and functional abnormalities in peripheral somatic nerves in rats with streptozocin (STZ)-induced diabetes. In the present studies, the effects of aminoguanidine treatment on ultrastructural 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 in diabetic rats, increased 9- to 11-fold in the superior mesenteric ganglia of 7- and 10-month STZ-diabetic rats compared with that in age-matched controls. Administration of aminoguanidine continuously from the time of induction of diabetes at a dose equal to or in excess of that providing a salutary effect in the diabetic somatic peripheral nervous 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 affect the ultrastructural appearance of neuroaxonal dystrophy in diabetic or age-matched control rat sympathetic ganglia after 7 or 10 months of continuous administration. Our findings (under these experimental conditions) do not support a role for aminoguanidine-sensitive processes 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 Amadori products) with intracellular and/or extracellular proteins and amine-containing lipids, superoxide anion generation during subsequent autoxidation of these glucose adducts, and nonglycative processes, remain potential pathogenetic mechanisms for diabetic autonomic neuropathy.

Original languageEnglish (US)
Pages (from-to)284-290
Number of pages7
JournalDiabetes
Volume45
Issue number3
StatePublished - Mar 1996
Externally publishedYes

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Neuroaxonal Dystrophies
Autonomic Ganglia
Sympathetic Ganglia
Experimental Diabetes Mellitus
Schiff Bases
Diabetic Neuropathies
Glucose
Advanced Glycosylation End Products
Autonomic Nervous System
Peripheral Nervous System
Glycosylated Hemoglobin A
Streptozocin
Peripheral Nerves
Nitric Oxide Synthase
Superoxides
Ganglia
Amines
pimagedine
Protein Isoforms
Urine

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Schmidt, R. E., Dorsey, D. A., Beaudet, L. N., Reiser, K. M., Williamson, J. R., & Tilton, R. (1996). Effect of aminoguanidine on the frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic autonomic ganglia of rats with streptozocin-induced diabetes. Diabetes, 45(3), 284-290.

Effect of aminoguanidine on the frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic autonomic ganglia of rats with streptozocin-induced diabetes. / Schmidt, Robert E.; Dorsey, Denise A.; Beaudet, Lucie N.; Reiser, Karen M.; Williamson, Joseph R.; Tilton, Ronald.

In: Diabetes, Vol. 45, No. 3, 03.1996, p. 284-290.

Research output: Contribution to journalArticle

Schmidt, RE, Dorsey, DA, Beaudet, LN, Reiser, KM, Williamson, JR & Tilton, R 1996, 'Effect of aminoguanidine on the frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic autonomic ganglia of rats with streptozocin-induced diabetes', Diabetes, vol. 45, no. 3, pp. 284-290.
Schmidt, Robert E. ; Dorsey, Denise A. ; Beaudet, Lucie N. ; Reiser, Karen M. ; Williamson, Joseph R. ; Tilton, Ronald. / Effect of aminoguanidine on the frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic autonomic ganglia of rats with streptozocin-induced diabetes. In: Diabetes. 1996 ; Vol. 45, No. 3. pp. 284-290.
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