Hyperglycemia and Diabetes — Induced Vascular Dysfunction: Role of Oxidative Stress

Pieper, Galen M.

doi:10.1007/978-1-4615-4649-8_16

Cited by 8 publications

(8 citation statements)

References 116 publications

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“…In addition, we have demonstrated that acetylcholine-induced vasodilation is decreased in epineurial arterioles from both streptozotocin-induced diabetic rats (an animal model of insulin deficiency and type 1 diabetes) and ZDF-fa/fa diabetic rats (an animal model of insulin resistance, hyperlipidemia, and type 2 diabetes) (Coppey et al 2000(Coppey et al , 2002Coppey, Gellett, Davidson, Dunlap, Lund, Salvemini et al 2001). Impaired endotheliumdependent vasodilation has been demonstrated in multiple vascular beds from different animal models of diabetes and in humans with type 1 or type 2 diabetes (Pieper 2000;Giugliano et al 1996;De Vriese, Verbeuren et al 2000). The mechanisms responsible for impaired vascular function in diabetes and how diabetes alters the biological activity of NO and EDHF are not well understood.…”

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confidence: 94%

Mediation of Vascular Relaxation in Epineurial Arterioles of the Sciatic Nerve: Effect of Diabetes in Type 1 and Type 2 Diabetic Rat Models

2003

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Previously, the authors have reported that acetylcholine-induced vascular relaxation in epineurial arterioles of the sciatic nerve is mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Furthermore, they have demonstrated that acetylcholine-induced vasodilation in these vessels is impaired in streptozotocin-induced (type 1) and ZDF obese (type 2) diabetic rats. In the present study, the authors sought to determine the effect of diabetes on NO- and EDHF-mediated vasodilation in epineurial arterioles. In epineurial arterioles from nondiabetic Sprague-Dawley rats, NO and EDHF are equivalent in regard to their contribution to acetylcholine-induced vascular relaxation. In contrast, NO accounts for a greater portion of acetylcholine-induced vascular relaxation in normal glycemic ZDF lean rats. Following 4 weeks of hyperglycemia, the EDHF component of acetylcholine-induced vascular relaxation was totally inhibited in both streptozotocin-induced and ZDF obese diabetic rats. Vasodilation mediated by NO was still active in epineurial arterioles from both type 1 and type 2 diabetic rat models. These data suggest that diabetes causes an impairment in EDHF-mediated vascular relaxation and that interventions directed at improving EDHF production or bioactivity may improve vascular function in epineurial arterioles in diabetes.

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confidence: 94%

Mediation of Vascular Relaxation in Epineurial Arterioles of the Sciatic Nerve: Effect of Diabetes in Type 1 and Type 2 Diabetic Rat Models

2003

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“…Studies using several types of diabetic rodent models have demonstrated impaired endothelial-dependent relaxation in both conduit and resistance arteries (4). Various factors have been proposed to contribute to this defect, including increased release of an endothelium-derived constricting factor, increased protein kinase C activity, inhibition of Na ϩ /K ϩ ATPase activity, a deficiency of substrate or cofactors for nitric oxide synthase, increased quenching of nitric oxide by advanced glycosylation end products, decreased nitric oxide release and decreased nitric oxide availability caused by increased quenching by superoxide, and subsequent formation of peroxynitrite (4). Studies showing that treatment with antioxidants prevents diabetes and hyperglycemia-induced impairment of endothelium-dependent relaxation suggest that oxidative stress is a major factor in the development of diabetic vascular disease (4,10 -23).…”

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confidence: 99%

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

et al. 2001

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We have shown that diabetes-induced reduction in endoneurial blood flow (EBF) and impaired endotheliumdependent vascular relaxation precede slowing of motor nerve conduction velocity (MNCV) and decreased sciatic nerve Na ؉ /K ؉ ATPase activity. Furthermore, vascular dysfunction was accompanied by an accumulation of superoxide in arterioles that provide circulation to the sciatic nerve. In the present study, we examined the effect that treatment of streptozotocin-induced diabetic rats with antioxidants has on vascular and neural function. Diabetic rats were treated with 0.5% ␣-lipoic acid as a diet supplement or with hydroxyethyl starch deferoxamine (HES-DFO) by weekly intravenous injections at a dose of 75 mg/kg. The treatments significantly improved diabetes-induced decrease in EBF, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic nerve, and MNCV. The treatments also reduced the production of superoxide by the aorta and superoxide and peroxynitrite by arterioles that provide circulation to the region of the sciatic nerve. Treating diabetic rats with ␣-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid-reactive substances in serum and significantly improved lens glutathione levels. In contrast, treating diabetic rats with HES-DFO did not prevent diabetes-induced changes of either of these markers of oxidative stress. Diabetes-induced increase in sciatic nerve conjugated diene levels was not improved by treatment with either ␣-lipoic acid or HES-DFO. Treating diabetic rats with ␣-lipoic acid but not HES-DFO partially improved sciatic nerve Na ؉ /K ؉ ATPase activity and myo-inositol content. The increase in sciatic nerve sorbitol levels in diabetic rats was unchanged by either treatment. These studies suggest that diabetes-induced oxidative stress and the generation of superoxide may be partially responsible for the development of diabetic vascular and neural complications.

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“…Both diabetes mellitus and hyperhomocysteinaemia (HH) are risk factors for cardiovascular disease (CVD) [1,2] and are associated with impaired endothelial nitric oxide and with excess superoxide (O 2 -) formation [3,4,5,6,7,8,9,10,11]. Clinically, there are now a number of studies indicating that homocysteine (Hcy) potentiates CVD in diabetic patients [2].…”

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confidence: 99%

“…Since reduced nitric oxide formation is associated with vascular disease [5,6], the pathogenic impact of Hcy could be mediated, in part, through an O 2 --mediated reduction of NO bioavailability [4,5]. Similarly, diabetes mellitus is also associated with impaired endothelial function and reduced nitric oxide formation as well as increased O 2 -generation by the vasculature [7,8,9,10,11].…”

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confidence: 99%

Homocysteine enhances impairment of endothelium-dependent relaxation and guanosine cyclic monophosphate formation in aortae from diabetic rabbits

et al. 2002

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Aims/hypothesis. Both diabetes mellitus and hyperhomocysteinaemia are risk factors for cardiovascular disease and are associated with impaired endothelial nitric oxide and with excess superoxide formation. To explore potential vasculopathic interactions between these risk factors, the effect of homocysteine on endothelium-dependent relaxation and cyclic GMP formation was investigated in aortae from diabetic rabbits. Methods. Rabbits were rendered diabetic by intravenous injection of alloxan. Six months later, the aortae were excised, cut into rings and mounted in an organ bath for isometric measurement of acetylcholineevoked relaxation in rings pre-contracted with phenylephrine. Cyclic GMP formation by aortic rings after stimulation with acetylcholine, calcium ionophore A23187 and sodium nitroprusside was assessed using radioimmunoassay. The effect of homocysteine on these parameters was then studied.Results. Ach-evoked relaxation and cyclic GMP formation induced with acetylcholine and calcium ionophore A23187 were impaired in aortae from diabetic rabbits compared with the control rabbits, effects that were reversed with superoxide dimutase (SOD) and augmented by 10-100 µmol/l homocysteine, an effect again reversed by SOD. Conclusion/interpretation. These data show that the bioavailability of nitric oxide is reduced in aortae from diabetic rabbits due to excess production of superoxide, an effect augmented by homocysteine. These results indicate that patients with diabetes mellitus could be susceptible to homocysteine-mediated angiopathy at lower concentrations than those that promote vasculopathy in non-diabetic patients. [Diabetologia (2002[Diabetologia ( ) 45:1325[Diabetologia ( -1331

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Hyperglycemia and Diabetes — Induced Vascular Dysfunction: Role of Oxidative Stress

Cited by 8 publications

References 116 publications

Mediation of Vascular Relaxation in Epineurial Arterioles of the Sciatic Nerve: Effect of Diabetes in Type 1 and Type 2 Diabetic Rat Models

Mediation of Vascular Relaxation in Epineurial Arterioles of the Sciatic Nerve: Effect of Diabetes in Type 1 and Type 2 Diabetic Rat Models

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

Homocysteine enhances impairment of endothelium-dependent relaxation and guanosine cyclic monophosphate formation in aortae from diabetic rabbits

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