The Effectiveness of Treatments of Diabetic Autonomic Neuropathy Is Not the Same in Autonomic Nerves Supplying Different Organs

The Effectiveness of Treatments of Diabetic Autonomic Neuropathy Is Not the Same in Autonomic Nerves Supplying Different Organs Hannah R. Shotton , Simon Clarke and Jill Lincoln From the Department of Anatomy and Developmental Biology, Autonomic Neuroscience Institute, Royal Free and University College Medical School, London, U.K. Abstract The aim of the study was to investigate antioxidant (α-lipoic acid [LA]) and γ-linolenic acid treatments in the prevention of changes in autonomic nerves induced in streptozotocin-diabetic rats. Autonomic nerves supplying the heart, penis, and gut were examined using immunohistochemical and biochemical techniques. LA and γ-linolenic acid (present in evening primrose oil [EPO]) were administered as dietary supplements (∼80 and 200 mg · kg −1 · day −1 , respectively). LA treatment prevented the diabetes-induced decrease of norepinephrine (NA) in the heart and of type I nitric oxide synthase (NOS-I) expression in erectile tissue of the penis but failed to prevent diabetes-induced changes in NA-, vasoactive intestinal polypeptide-, or calcitonin gene-related peptide-containing nerves supplying the ileum. LA partially prevented and EPO totally prevented the increase in NOS-I activity induced by diabetes in the ileum. EPO treatment failed to prevent any other diabetes-induced changes in the heart, penis, or ileum. These results demonstrate that, whereas LA treatment is more effective than EPO in preventing diabetes-induced changes in autonomic nerves, the effectiveness of LA treatment varies with the target organ studied. Diabetes-induced changes in nerves supplying the ileum are more resistant to treatment than those of the heart and penis. Footnotes Address correspondence and reprint requests to Dr. Jill Lincoln, Autonomic Neuroscience Institute, Royal Free and University College Medical School, Rowland Hill St., London NW3 2PF, U.K. E-mail: j.lincoln{at}ucl.ac.uk . Received for publication 8 August 2002 and accepted in revised form 23 September 2002. CGRP, calcitonin gene-related peptide; DHBA, dihydroxybenzylamine; EPO, evening primrose oil; EPOC, EPO-treated control; EPOD, EPO-treated diabetic; HPLC-ECD, high-performance liquid chromatography with electrochemical detection; LA, α-lipoic acid; LAC, LA-treated control; LAD, LA-treated diabetic; NA, norepinephrine; NOS-I, type I nitric oxide synthase; PCA, perchloric acid; ROS, reactive oxygen species; TH, tyrosine hydroxylase; UC, untreated control; UD, untreated diabetic;