Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals.
Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg.kg-1.day-1), group II received STZ plus AG (50 mg.kg-1.day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.
Kihara
M
M
Department of Neurology, Mayo Foundation, Rochester, MN 55905.
Schmelzer
J D
JD
Poduslo
J F
JF
Curran
G L
GL
Nickander
K K
KK
Low
P A
PA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004594:Electrophysiology; D005609:Free Radicals; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000294:innervation / Q000502:physiology / Q000503:physiopathology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D005609:Free Radicals; D006146:Guanidines; D010100:Oxygen; C004479:pimagedine