Effect of Antioxidant Treatment of Streptozotocin-Induced Diabetic Rats on Endoneurial Blood Flow, Motor Nerve Conduction Velocity, and Vascular Reactivity of Epineurial Arterioles of the Sciatic Nerve

Previously we have demonstrated that diabetes causes impairment in vascular function of epineurial vessels, which precedes the slowing of motor nerve conduction velocity. Treatment of diabetic rats with aldose reductase inhibitors, aminoguanidine or myo-inositol supplementation have been shown to improve motor nerve conduction velocity and/or decreased endoneurial blood flow. However, the effect these treatments have on vascular reactivity of epineurial vessels of the sciatic nerve is unknown. In these studies we examined the effect of treating streptozotocin-induced rats with sorbinil, aminoguanidine or myo-inositol on motor nerve conduction velocity, endoneurial blood flow and endothelium dependent vascular relaxation of arterioles that provide circulation to the region of the sciatic nerve. Treating diabetic rats with sorbinil, aminoguanidine or myo-inositol improved the reduction of endoneurial blood flow and motor nerve conduction velocity. However, only sorbinil treatment significantly improved the diabetes-induced impairment of acetylcholinemediated vasodilation of epineurial vessels of the sciatic nerve. All three treatments were efficacious in preventing the appropriate metabolic derangements associated with either activation of the polyol pathway or increased nonenzymatic glycation. In addition, sorbinil was shown to prevent the diabetes-induced decrease in lens glutathione level. However, other markers of oxidative stress were not vividly improved by these treatments. These studies suggest that sorbinil treatment may be more effective in preventing neural dysfunction in diabetes than either aminoguanidine or myoinositol.

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Effect of M40403 treatment of diabetic rats on endoneurial blood flow, motor nerve conduction velocity and vascular function of epineurial arterioles of the sciatic nerve

British Journal of Pharmacology ◽

10.1038/sj.bjp.0704216 ◽

2001 ◽

Vol 134 (1) ◽

pp. 21-29 ◽

Cited By ~ 68

Author(s):

Lawrence J Coppey ◽

Jill S Gellett ◽

Eric P Davidson ◽

Joyce A Dunlap ◽

Donald D Lund ◽

...

Keyword(s):

Blood Flow ◽

Sciatic Nerve ◽

Nerve Conduction ◽

Vascular Function ◽

Nerve Conduction Velocity ◽

Motor Nerve ◽

Diabetic Rats ◽

Motor Nerve Conduction Velocity ◽

Motor Nerve Conduction ◽

Endoneurial Blood Flow

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Reduction of cyclic AMP in the sciatic nerve of rats made diabetic with streptozotocin and the mechanism involved

Journal of Endocrinology ◽

10.1677/joe.0.1360431 ◽

1993 ◽

Vol 136 (3) ◽

pp. 431-438 ◽

Cited By ~ 14

Author(s):

H. Shindo ◽

M. Tawata ◽

T. Onaya

Keyword(s):

Sciatic Nerve ◽

Cyclic Amp ◽

Nerve Conduction Velocity ◽

Motor Nerve ◽

Diabetic Rats ◽

Motor Nerve Conduction Velocity ◽

Nerve Function ◽

Camp Content ◽

Motor Nerve Conduction ◽

Sciatic Nerves

ABSTRACT We have investigated the relationship between cyclic nucleotides and nerve function in the sciatic nerve of rats made diabetic with streptozotocin. Cyclic AMP (cAMP) content in the sciatic nerves of diabetic rats was significantly (P < 0·05) lower than in those of normal rats, while cyclic GMP content did not differ between the two groups. Administration of the stable prostacyclin analogue iloprost or dibutyryl cyclic AMP (dbcAMP) significantly (P<0·05) restored the cAMP content in the sciatic nerves and motor nerve conduction velocity, which reflects nerve function. There was a positive correlation between cAMP content in the sciatic nerves and motor nerve conduction velocity in both normal and diabetic rats. Endoneurial preparations of sciatic nerves obtained from normal rats were incubated in Krebs–Ringer bicarbonate buffer containing d-glucose (30 or 5·5 mmol/l). Cyclic AMP accumulation was significantly (P<0·05) suppressed in the buffer containing 30 mmol d-glucose/l compared with that containing 5·5 mmol/l. Iloprost (P<0·05) and dbcAMP (P<0·01) increased cAMP accumulations in the tissues incubated in buffer containing both 5·5 and 30 mmol d-glucose/l. When non-metabolizing hexoses, such as l-glucose or 3-O-methylglucose instead of d-glucose were used, cAMP accumulations at 30 mmol hexose/1 were not significantly different from those at 5·5 mmol/l. Cyclic AMP phosphodiesterase activity in the sciatic nerves of diabetic rats did not change compared with that in nerves from normal rats. Although not significant, mean ATP content in the sciatic nerves of diabetic rats was about 30% lower than that in nerves of normal rats. Basal, iloprost-stimulated and forskolin-stimulated adenylate cyclase activities in the sciatic nerves of diabetic rats were significantly (P<0·05) reduced when compared with those of control rats. We therefore conclude that reduction of cAMP content in peripheral nerves may be involved in the pathogenesis of diabetic neuropathy and is mainly caused by the impairment of adenylate cyclase activity in the diabetic state. Journal of Endocrinology (1993) 136, 431–438

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Slowing of Motor Nerve Conduction Velocity in Streptozotocin-induced Diabetic Rats is Preceded by Impaired Vasodilation in Arterioles that Overlie the Sciatic Nerve

International Journal of Experimental Diabetes Research ◽

10.1155/edr.2000.131 ◽

2000 ◽

Vol 1 (2) ◽

pp. 131-143 ◽

Cited By ~ 89

Author(s):

Lawrence J. Coppey ◽

Eric P. Davidson ◽

Joyce A. Dunlap ◽

Donald D. Lund ◽

Mark A. Yorek

Keyword(s):

Blood Flow ◽

Sciatic Nerve ◽

Conduction Velocity ◽

Nerve Conduction ◽

Vascular Function ◽

Nerve Conduction Velocity ◽

Motor Nerve ◽

Motor Nerve Conduction Velocity ◽

Diabetic Rat ◽

Motor Nerve Conduction

Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function in arterioles that provide circulation to the region of the sciatic nerve is associated with reduced endoneural blood flow (EBF) and that these defects precede slowing of motor nerve conduction velocity, and thereby may contribute to nerve dysfunction. As early as three days after the induction of diabetes endoneural blood flow was reduced in the STZ-induced diabetic rat. Furthermore, after 1 week of diabetes acetylcholine-induced vasodilation was found to be impaired. This was accompanied by an increase in the superoxide level in arterioles that provide circulation to the region of the sciatic nerve as well as changes in the level of other markers of oxidative stress including an increase in serum levels of thiobarbituric acid reactive substances and a decrease in lens glutathione level. In contrast to the vascular related changes that occur within 1 week of diabetes, motor nerve conduction velocity and sciatic nerveNa+/k+ATPase activity were significantly reduced following 2 and 4 weeks of diabetes, respectively. These studies demonstrate that changes in vascular function in the STZ-induced diabetic rat precede the slowing of motor nerve conduction velocity (MNCV) and are accompanied by an increase in superoxide levels in arterioles that provide circulation to the region of the sciatic nerve.

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