Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans

Beckman, Joshua A.; Goldfine, Allison B.; Gordon, Mary Beth; Creager, Mark A.

doi:10.1161/01.cir.103.12.1618

Cited by 281 publications

(218 citation statements)

References 46 publications

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“…Rather surprisingly, the results of these studies are not consistent [17,19] despite the fact that hyperinsulinaemia itself has been claimed to have a selective, major negative effect on this segment of the vascular tree [39,40]. The evidence in resistance vessels is scarce [22,41], comes from a single laboratory and describes an inhibitory effect that is small (ACh response reduced by 20%), only detectable for unphysiological degrees of hyperglycaemia (over 16 mmol/l) maintained for 6 h and effectively prevented by a very small gradient (35 pmol/l) of hyperinsulinaemia. Other laboratories have reached opposite conclusions.…”

Section: Discussionmentioning

confidence: 90%

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

et al. 2008

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Aims/hypothesis Hyperglycaemia and hyperinsulinaemia have opposite effects on endothelium-dependent vasodilatation in microcirculation, but the net effect elicited by glucose ingestion and the separate influence of glucose tolerance are unknown. Methods In participants with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or diabetic glucose tolerance, multiple plasma markers of both oxidative stress and endothelial activation, and forearm vascular responses (plethysmography) to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) infusions were measured before and after glucose ingestion. In another IGT group, we evaluated the time-course of the skin vascular responses (laser Doppler) to ACh and SNP (by iontophoresis) 1, 2 and 3 h into the OGTT; the plasma glucose profile was then reproduced by means of a variable intravenous glucose infusion and the vascular measurements repeated. Results Following oral glucose, plasma antioxidants were reduced by 5% to 10% (p<0.01) in all patient groups. The response to acetylcholine was not affected by glucose ingestion in any group, while the response to SNP was attenuated, particularly in the IGT group. The ACh:SNP ratio was slightly improved therefore in all groups, even in diabetic participants, in whom it was impaired basally. A time-dependent improvement in ACh:SNP ratio was also observed in skin microcirculation following oral glucose; this improvement was blunted when matched hyperglycaemia was coupled with lower hyperinsulinaemia (intravenous glucose). Conclusions/interpretation Regardless of glucose tolerance, oral glucose does not impair endothelium-dependent vasodilatation either in resistance arteries or in the microcirculation, despite causing increased oxidative stress; the endogenous insulin response is probably responsible for countering any inhibitory effect on vascular function.

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Section: Discussionmentioning

confidence: 90%

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

et al. 2008

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“…It has been reported that infusion with vitamin C leads to an increase in forearm blood flow of 1 . 4 ml/100 ml per min in subjects after a 6 h hyperglycaemic clamp (36) . Vitamin C supplementation has been shown to improve endothelium-dependent vasodilation, measured by flow-mediated dilation, from 4 .…”

Section: Carotenoids: Flavonoids: Cvd: Laser Doppler Imagingmentioning

confidence: 92%

Effects of chronic and acute consumption of fruit- and vegetable-puree-based drinks on vasodilation, risk factors for CVD and the response as a result of theeNOSG298T polymorphism

et al. 2009

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The average UK adult consumes less than three portions of fruit and vegetables daily, despite evidence to suggest that consuming five portions daily could help prevent chronic diseases. It is recommended that fruit juice should only count as one of these portions, as juicing removes fibre and releases sugars. However, fruit juices contain beneficial compounds such as vitamin C and flavonoids and could be a useful source of dietary phytochemicals. Two randomised controlled cross-over intervention studies investigating the effects of chronic and acute consumption of commercially-available fruit-and vegetable-puree-based drinks (FVPD) on bioavailability, antioxidant status and CVD risk factors are described. Blood and urine samples were collected during both studies and vascular tone was measured using laser Doppler imaging. In the chronic intervention study FVPD consumption was found to significantly increase dietary carotenoids (P = 0 . 001) and vitamin C (P = 0 . 003). Plasma carotenoids were increased (P = 0 . 001), but the increase in plasma vitamin C was not significant. There were no significant effects on oxidative stress, antioxidant status and other CVD risk factors. In the acute intervention study FVPD were found to increase total plasma nitrate and nitrite (P = 0 . 001) and plasma vitamin C (P = 0 . 002). There was no effect on plasma lipids or uric acid, but there was a lower glucose and insulin peak concentration after consumption of the FVPD compared with the sugar-matched control. There was a trend towards increased vasodilation following both chronic and acute FVPD consumption. All volunteers were retrospectively genotyped for the eNOS G298T polymorphism and the effect of genotype on the measurements is discussed. Overall, there was a non-significant trend towards increased endothelium-dependent vasodilation following both acute and chronic FVPD consumption. However, there was a significant time · treatment effect (P < 0 . 05) of acute FVPD consumption in individuals with the GG variant of the eNOS gene. Carotenoids: Flavonoids: CVD: Laser Doppler imagingCVD is one of the major causes of death in Europe and is responsible for 4 . 3 · 10 6 deaths each year across the continent (1) . One of the emerging risk factors for CVD is dysfunction of the endothelium (2,3) , which is characterised by a reduction in the bioavailability of vasodilators, predominantly NO, endothelium-derived hyperpolarizing factor and prostacyclin, and an increase in endothelium-derived vasoconstrictors, e.g. thromboxane A 2 , PGH 2 and endothelin 1 (2) . Endothelial dysfunction can be assessed by measuring enhanced and maintained endothelial activation and impaired endothelium-dependent vasodilation (4) .Endothelial activation is determined by an increase in the plasma concentrations of soluble cell adhesion molecules, such as intercellular adhesion molecule-1, vascularAbbreviations: atRA, all-trans-retinoic acid; eNOS, endothelial NO synthase; FVPD, fruit-and vegetable-puree-based drinks.

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“…While the vasodilating effects of insulin are established [9,10], the direct vascular actions of short-term hyperglycaemia are largely unknown. Studies investigating the effects of high glucose on macrovascular and microvascular perfusion have yielded conflicting results: some have shown attenuated vasodilation [11,12,13,14,15,16], some have demonstrated enhanced vasodilation [17,18,19,20], whereas others found no changes in vascular tone [21,22,23]. The present study was designed to gain deeper insights into the immediate effects of high glucose on endothelial NO formation and vascular tone, and its stimulatory role on the vascular effects of insulin.…”

Section: Introductionmentioning

confidence: 96%

Acute effects of glucose and insulin on vascular endothelium

et al. 2004

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Aims/hypothesis. Chronic exposure to high concentrations of glucose has consistently been demonstrated to impair endothelium-dependent, nitric oxide (NO)-mediated vasodilation. In contrast, several clinical investigations have reported that acute exposure to high glucose, alone or in combination with insulin, triggers vasodilation. The aim of this study was to examine whether elevated glucose itself stimulates endothelial NO formation or enhances insulin-mediated endothelial NO release. Methods. We measured NO release and vessel tone ex vivo in porcine coronary conduit arteries (PCAs). Intracellular Ca 2+ was monitored in porcine aortic endothelial cells (PAECs) by fura-2 fluorescence. Expression of the Na + /glucose cotransporter-1 (SGLT-1) was assayed in PAECs and PCA endothelium by RT-PCR. Results. Stimulation of PCAs with D-glucose, but not the osmotic control L-glucose, induced a transient increase in NO release (EC 50 ≈10 mmol/l), mediated by a rise in intracellular Ca 2+ levels due to an influx from the extracellular space. This effect was abolished by inhibitors of the plasmalemmal Na + /Ca 2+ exchanger (dichlorobenzamil) and the SGLT-1 (phlorizin), which was found to be expressed in aortic and coronary endothelium. Alone, D-glucose did not relax PCA, but did augment the effect of insulin on NO release and vasodilation. Conclusions/interpretation. An increased supply of extracellular D-glucose appears to enhance the activity of the endothelial isoform of nitric oxide synthase by increasing intracellular Na + concentrations via SGLT-1, which in turn stimulates an extracellular Ca 2+ influx through the Na + /Ca 2+ exchanger. This mechanism may be responsible for glucose-enhanced, insulin-dependent increases in tissue perfusion (including coronary blood-flow), thus accelerating glucose extraction from the blood circulation to limit the adverse vascular effects of prolonged hyperglycaemia.

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Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans

Abstract: Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion.

Cited by 281 publications

References 46 publications

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

Effects of glucose tolerance on the changes provoked by glucose ingestion in microvascular function

Effects of chronic and acute consumption of fruit- and vegetable-puree-based drinks on vasodilation, risk factors for CVD and the response as a result of theeNOSG298T polymorphism

Acute effects of glucose and insulin on vascular endothelium

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