title: Cardiovascular autonomic neuropathy in spontaneously diabetic rats with and without application of EGb 761.
abstract: Cardiovascular autonomic neuropathy causes abnormalities in the diabetic heart with various clinical sequelae, including exercise intolerance, arrhythmias and painless myocardial infarction. Little is known about (ultra)structural alterations of the myocardial nervous network. On the assumption that this diabetes-specific neuropathy develops due to permanently increased oxidative stress by liberation of oxygen-free radicals, adjuvant application of antioxidative therapeutics appears promising in preventing or delaying long-term diabetic complications. We have investigated the effects of Ginkgo biloba extract (EGb 761), a radical scavenger, against diabetes-induced myocardial nervous damage in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats. Morphological and morphometric parameters were evaluated by electron microscopy. We used immunohistochemistry to investigate protein expression of protein gene product 9.5, S100 protein, and thyroxin hydroxylase as a neuronal marker. Alterations of cardiac sympathetic activity were measured using the in vivo 123I-metaiodobenzyl-guanidine imaging, and the immunofluorescent labeling of beta1-adrenergic receptors and adenylate cyclase. Our results revealed that A) Diabetes results in slight to moderate ultrastructural alterations (hydrops, disintegration of substructure) of autonomic nerve fibers and related Schwann cells in untreated BB diabetic rats; B) Cardiac sympathetic integrity and activity is impaired due to alterations in the presynaptic nerve terminals and the postsynaptic ß1-AR-AC coupling system; C) Pre-treatment of diabetic myocardium with EGb results in an improvement of most of these parameters compared to unprotected myocardium. In conclusion, EGb may act as a potent therapeutic adjuvant in diabetics with respect to cardiovascular autonomic neuropathy, which may contribute to the prevention of late complications in diabetes.
authors.affiliation: Department of Surgery II, University of Leipzig, Leipzig, Germany. rick.schneider@medizin.uni-leipzig.de
authors.forename: Rick
authors.initials: R
authors.lastname: Schneider
authors.forename: Klaus
authors.initials: K
authors.lastname: Welt
authors.forename: Wolfram
authors.initials: W
authors.lastname: Aust
authors.forename: Regina
authors.initials: R
authors.lastname: Kluge
authors.forename: Heinz
authors.initials: H
authors.lastname: Löster
authors.forename: Günther
authors.initials: G
authors.lastname: Fitzl
mesh_terms: D019797:3-Iodobenzylguanidine; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000473:pathology*; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D003929:Diabetic Neuropathies / Q000000981:diagnostic imaging / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020441:Ginkgo biloba; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000648:ultrastructure; D010936:Plant Extracts / Q000494:pharmacology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D000096983:Ginkgo Extract
chemical_list: D019797:3-Iodobenzylguanidine; D016166:Free Radical Scavengers; D010936:Plant Extracts; D019275:Radiopharmaceuticals; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract