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 experimen tal diabetes (streptozotocin-induced; 8-10 weeks duration). The contri bution of endoneurial vasoactive nitric oxide to the LDF of these anim als was also investigated by the direct micro-injection of N-G-nitro-L -arginine methyl ester (L-NAME; 1 nmol in 1 mu l), followed by L-argin ine (100 nmol in 1 mu l), into the sciatic nerve endoneurium. 2 The MN CV (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 g l(-1)), diabetics (37.4 +/-4.1). 3 L-NAME markedly reduced the resting LDF (arbitrary units; m ean+/-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 (t o 145+/-12; P<0.001). 4 AG treatment increased the resting LDF of cont rol (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 treatm ent may affect nitric oxide production in the vasa nervorum of periphe ral nerves. However, the effects of AG-treatment are not consistent wi th the prevention of a diabetes-associated reduction in endoneurial ni tric oxide production. The mechanisms by which AG attenuates nerve con duction slowing in streptozotocin-diabetic rats therefore remain uncle ar.