Effect of aminoguanidine treatment on diabetes-induced changes in the myenteric plexus of rat ileum.
The aim of this study was to investigate the ability of aminoguanidine (AG) to prevent diabetes-induced changes in nitric oxide synthase- (nNOS), vasoactive intestinal polypeptide- (VIP) and noradrenaline- (NA) containing nerves of the rat ileum using immunohistochemical and biochemical techniques. Diabetes was induced in adult male Wistar rats by a single intraperitoneal injection of streptozotocin (65 mg/kg). AG was administered in the drinking water to control (1.8 g/l) and diabetic (0.9 g/l) rats over a period of 8 weeks. Diabetes caused a significant increase in the thickness of nNOS-containing nerve fibres (p<0.001) in the circular muscle, in nNOS activity (p<0.05) and in the size distribution of nNOS-containing myenteric neurons (p<0.001). The thickness of VIP-containing nerve fibres was significantly greater (p<0.01) and there was a significant increase in varicosity size (p<0.01) and proportion of VIP-positive myenteric neurons (p<0.01) in diabetes. NA levels were significantly reduced (p<0.01) and the size of varicosities containing tyrosine hydroxylase (TH) was significantly increased (p<0.001) in diabetes. AG treatment completely or partially prevented the diabetes-induced increase in nNOS activity, in VIP-containing varicosity size, and in fibre width of both VIP- and nNOS-containing fibres in the circular muscle but had no effect on the diabetes-induced increase in nNOS-containing neuronal size or proportion of VIP-containing myenteric neurons. In contrast to VIP, AG treatment had no effect on the increase in TH-containing varicosity size in diabetes and also failed to prevent the decrease in NA levels induced by diabetes. These results indicate that AG treatment for neuropathy is not equally effective for all autonomic nerves supplying the ileum and that diabetes-induced changes in NA-containing nerves are particularly difficult to treat.
Shotton
Hannah R
HR
Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
Adams
Ashok
A
Lincoln
Jill
J
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000473:pathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014660:Vasoactive Intestinal Peptide / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D006146:Guanidines; D014660:Vasoactive Intestinal Peptide; D052248:Nitric Oxide Synthase Type I; C004479:pimagedine; D009638:Norepinephrine