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

Coppey, Lawrence J.; Davidson, Eric P.; Dunlap, Joyce A.; Lund, Donald D.; Yorek, Mark A.

doi:10.1155/edr.2000.131

Cited by 134 publications

(206 citation statements)

References 45 publications

Supporting

Mentioning

188

Contrasting

Order By: Relevance

“…In our studies, however, we did not detect induction of iNOS in the penis or pyloric sphincter of diabetic rats or in the SH-SY5Y cells when exposed to RA or AGEs (S. Cellek, unpublished observations). Peroxynitrite, the product of the reaction between NO and superoxide in arterioles that provide circulation to the sciatic nerve, has been suggested to be involved in diabetic neuropathy [45,46]. Although we did not detect any increase in nitrotyrosine immunostaining in diabetic rat penis [4], we cannot exclude the possibility that eNOS from nearby blood vessels could produce NO, leading to nitrergic degeneration.…”

Section: Discussioncontrasting

confidence: 72%

Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: A new insight into selective nitrergic neuropathy in diabetes

et al. 2004

View full text Add to dashboard Cite

Aims/hypothesis. We have previously shown that in diabetes nitrergic neurones innervating the urogenital and gastrointestinal organs undergo a selective degenerative process. This comprises an initial insulin-reversible decrease in neuronal nitric oxide synthase (nNOS) in the axons, followed by apoptosis of the nitrergic neurones, a process that is not reversible by insulin. Since apoptosis was independent of serum glucose concentrations, and advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic complications, we have now measured AGEs in the serum and penis, pyloric sphincter and pelvic ganglia of diabetic animals at different times after streptozotocin treatment. Furthermore, we have studied their effect in vitro on human neuroblastoma (SH-SY5Y) cells in the presence or absence of nNOS expression. Methods. Serum AGEs were measured using fluorometry and ELISA. Accumulation of AGEs in the tissues was evaluated with immunohistochemistry. The viability, apoptosis and oxidative stress in SH-SY5Y cells were measured upon exposure to AGEs or high concentrations of glucose. Results. AGEs increased gradually in the serum and tissues of streptozotocin-induced diabetic rats; this process was not affected by delayed insulin treatment. In SH-SY5Y cells, AGEs, but not high glucose concentrations, increased the reactive oxygen species and caspase-3-dependent apoptosis in a synergistic fashion with endogenous nitric oxide (NO). Apoptosis was prevented by treatment with a NOS inhibitor, a pan-caspase inhibitor, a soluble receptor of AGEs or an anti-oxidant, but not an inhibitor of soluble guanylate cyclase. Conclusions/interpretation. The synergistic actions of NO and AGEs account for the irreversible nitrergic degeneration in diabetes. [Diabetologia (2004) 47: 331-339]

show abstract

Section: Discussioncontrasting

confidence: 72%

Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: A new insight into selective nitrergic neuropathy in diabetes

et al. 2004

View full text Add to dashboard Cite

show abstract

“…In their studies, they showed that nerve blood flow was reduced as early as 1 week after diabetes induction. Moreover, Wright and Nukada, and our laboratory have shown that reductions in nerve blood flow preceded the decrease in nerve conduction velocities [34,35]. In addition, we have shown that endothelial-dependent vasodilation of arterioles that provide circulation to the region of the sciatic nerve is impaired by diabetes and the reduction in vascular function also precedes slowing of motor nerve conduction velocity [35,36].…”

supporting

confidence: 52%

“…Moreover, Wright and Nukada, and our laboratory have shown that reductions in nerve blood flow preceded the decrease in nerve conduction velocities [34,35]. In addition, we have shown that endothelial-dependent vasodilation of arterioles that provide circulation to the region of the sciatic nerve is impaired by diabetes and the reduction in vascular function also precedes slowing of motor nerve conduction velocity [35,36]. These studies suggest that vascular dysfunction is an important factor underlying nerve conduction deficits and reduced endoneurial blood flow early in the development of diabetic neuropathy.…”

Section: Introductionmentioning

confidence: 84%

“…Hydroethidine (Molecular Probes Inc., Eugene, OR), an oxidative fluorescent dye, was used to evaluate in situ levels of superoxide (O 2 -) as described previously [35,52]. Hydroethidine is permeable to cells and in the presence of O 2 -is oxidized to fluorescent ethidium bromide, where it is trapped by intercalating with DNA.…”

Section: Detection Of Superoxidementioning

confidence: 99%

“…Treating diabetic rats with myo-inositol or aminoguanidine did not improve the decrease in lens glutathione level induced by diabetes. In contrast, treating diabetic rats with sorbinil significantly improved lens glutathione level.We have previously reported that diabetes causes an increase in superoxide level in arterioles that provide circulation to the region of the sciatic nerve [35]. The increase in superoxide level was observed in endothelial cells as well as in the smooth muscle and adventitial cells.…”

mentioning

confidence: 92%

See 2 more Smart Citations

Effect of Treating Streptozotocin‐Induced Diabetic Rats With Sorbinil, Myo‐Inositol or Aminoguanidine on Endoneurial Blood Flow, Motor Nerve Conduction Velocity and Vascular Function of Epineurial Arterioles of the Sciatic Nerve

Coppey

Gellett

Davidson

et al. 2001

Journal of Diabetes Research

Self Cite

View full text Add to dashboard Cite

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 streptozotocininduced rats with sorbinil, aminoguanidine or myo-inositol on motor nerve conduction velocity, endoneurial blood flow and endotheliumdependent 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 mark-____________________ *Corresponding author: 3 E 17 Veterans Affairs Medical Center, Iowa City, IA 52246; tel: (319) 338-0581 ext. 7629; fax: (319) 339-7025; e-mail: myorek@icva.gov Int. Jnl. Experimental Diab. Res., 3:21-36, 2002 © 2002 Taylor and Francis 1560 ers 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.Key words: diabetes, diabetic neuropathy, endothelium, vascular reactivity, aldose reductase inhibitor, aminoguanidine INTRODUCTIONDiabetic neuropathy is a multifactorial problem likely due to the poor control of hyperglycemia. Two of these perturbations are the activation of the polyol pathway by which glucose is metabolized to sorbitol via aldose reductase contributing to an alteration in the redox balance and a decrease in myo-inositol uptake and content and an increase in non-enzymatic glycation leading to the abnormal glycation of proteins [1,2]. In animal models of diabetes prevention of these defects by treatment with aldose reductase inhibitors, aminoguanidine or supplementation with myo-inositol has been shown to improve peripheral neuropathy.Studies from numerous laboratories have shown that treating diabetic rats with an aldose reductase inhibitor improves nerve function as well as endoneurial blood flow [3][4][5][6][7][8][9][10][11][12]. This has led to wide speculation regarding the potential benefit of aldose reductase inhibitor treatment of diabetic complications [10][11][12][13][14][15][16]. However, clinical tri...

show abstract

Diet‐induced obesity in Sprague–Dawley rats causes microvascular and neural dysfunction

Davidson

Coppey

Calcutt

et al. 2010

Diabetes Metabolism Res

Self Cite

View full text Add to dashboard Cite

show abstract

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

Cited by 134 publications

References 45 publications

Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: A new insight into selective nitrergic neuropathy in diabetes

Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: A new insight into selective nitrergic neuropathy in diabetes

Effect of Treating Streptozotocin‐Induced Diabetic Rats With Sorbinil, Myo‐Inositol or Aminoguanidine on Endoneurial Blood Flow, Motor Nerve Conduction Velocity and Vascular Function of Epineurial Arterioles of the Sciatic Nerve

Diet‐induced obesity in Sprague–Dawley rats causes microvascular and neural dysfunction

Contact Info

Product

Resources

About