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Aminoguanidine--effects on endoneurial vasoactive nitric oxide and on motor nerve conduction velocity in control and streptozotocin-diabetic rats. 1997

M Dewhurst, and N Omawari, and D R Tomlinson
Department of Pharmacology, St. Bartholomew's, London.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009431 Neural Conduction The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus. Nerve Conduction,Conduction, Nerve,Conduction, Neural,Conductions, Nerve,Conductions, Neural,Nerve Conductions,Neural Conductions
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006146 Guanidines A family of iminourea derivatives. The parent compound has been isolated from mushrooms, corn germ, rice hulls, mussels, earthworms, and turnip juice. Derivatives may have antiviral and antifungal properties.
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D006631 Amine Oxidase (Copper-Containing) A group of enzymes including those oxidizing primary monoamines, diamines, and histamine. They are copper proteins, and, as their action depends on a carbonyl group, they are sensitive to inhibition by semicarbazide. Diamine Oxidase,Histaminase,Amine Oxidase, Copper-Containing,Copper Amine Oxidase,Diaminobenzidine Oxidase,Semicarbazide-Sensitive Amine Oxidase,Xylylene Diamine Oxidase,Amine Oxidase, Copper,Amine Oxidase, Copper Containing,Amine Oxidase, Semicarbazide-Sensitive,Copper-Containing Amine Oxidase,Diamine Oxidase, Xylylene,Oxidase, Copper Amine,Oxidase, Copper-Containing Amine,Oxidase, Diamine,Oxidase, Diaminobenzidine,Oxidase, Semicarbazide-Sensitive Amine,Oxidase, Xylylene Diamine,Semicarbazide Sensitive Amine Oxidase

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