Aminoguanidine--effects on endoneurial vasoactive nitric oxide and on motor nerve conduction velocity in control and streptozotocin-diabetic rats.
1. The effects of aminoguanidine (AG) treatment on reductions in motor nerve conduction velocity (MNCV) and sciatic nerve blood flow, indexed by laser Doppler flux (LDF), were investigated in rats with experimental diabetes (streptozotocin-induced; 8-10 weeks duration). The contribution of endoneurial vasoactive nitric oxide to the LDF of these animals was also investigated by the direct micro-injection of NG-nitro-L-arginine methyl ester (L-NAME; 1 nmol in 1 microliter), followed by L-arginine (100 nmol in 1 microliter), into the sciatic nerve endoneurium. 2. The MNCV (m s-1, mean +/- 1 s.d.) of diabetic rats (38.2 +/- 1.5) was lower (P < 0.01) than that of age-matched controls (47.2 +/- 4.2). AG treatment (50 mg kg-1 day-1, i.p.) attenuated the diabetes-induced deficits in MNCV (43.4 +/- 5.9; P < 0.01), but had no effect in controls (48.8 +/- 3.8) or, if administered via drinking water (1 gl-1), diabetics (37.4 +/- 4.1). 3. L-NAME markedly reduced the resting LDF (arbitrary units; mean +/- s.e.mean) of controls (209 +/- 13 to 120 +/- 18; P < 0.005), an effect reversed by subsequent L-arginine (to 206 +/- 27). In diabetic rats the LDF reduction following L-NAME was much smaller (111 +/- 11 to 84 +/- 6; P < 0.05), but the change with L-arginine was significantly increased (to 145 +/- 12; P < 0.001). 4. AG treatment increased the resting LDF of control (265 +/- 34) and diabetic rats (133 +/- 14 for daily injection and 119 +/- 13 for drinking water). The responses to L-NAME and L-arginine were not changed markedly by AG treatment. However, L-arginine appeared to be less effective. 5. In conclusion, these data suggest that AG treatment may affect nitric oxide production in the vasa nervorum of peripheral nerves. However, the effects of AG-treatment are not consistent with the prevention of a diabetes-associated reduction in endoneurial nitric oxide production. The mechanisms by which AG attenuates nerve conduction slowing in streptozotocin-diabetic rats therefore remain unclear.
Dewhurst
M
M
Department of Pharmacology, St. Bartholomew's, London.
Omawari
N
N
Tomlinson
D R
DR
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose; D001794:Blood Pressure; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009431:Neural Conduction / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects*; D013311:Streptozocin
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006146:Guanidines; D013311:Streptozocin; D001120:Arginine; D019001:Nitric Oxide Synthase; D006631:Amine Oxidase (Copper-Containing); C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester