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P. P. Connell, T. Walshe, G. Ferguson, G. Ferguson, W. Gao, C. J. O' Brien, P. A. Cahill; Elevated Glucose Attenuates Agonist-and Flow Stimulated Nitric Oxide Activity in Microvascular Retinal Endothelial. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1388. doi: https://doi.org/.
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Impaired vasoactive release of opposing vasodilator and vasoconstrictor mediators due to endothelial dysfunction is integral to the pathogenesis of diabetic retinopathy. The aim of this study was to determine the effect of hyperglycaemia on the expression and release of NO in ECs under both static (basal and acetylcholine stimulated) and flow stimulated (laminar shear stress (10 dynes/cm2) and pulsatile flow (0.3-23.0 dynes/cm2) using a laminar shear apparatus and an in vitro perfused transcapillary culture. Methods; Endothelial nitric oxide synthase (eNOS) expression and activity, measured by immunoblot and nitrate levels, respectively, was determined following exposure of bovine retinal microvacsular endothelial cells (BREC) to varying concentrations of glucose (0-16 mM) under static and acetycholine-stimulated conditons. The influence of glucose on laminar shear stress (10 dynes/cm2) and pulsatile flow (0.3 - 23 dynes/cm2) induced changes in NO was also examined using a laminar shear apparatus and an in vitro perfused transcapillary culture system.
The expression of eNOS decreased by 25.0± 6.0% and 55±3.4% in 11 and 16 mM glucose, respectively concomitant with a significant dose dependent decrease in the release of NO in static cells. Acetylcholine stimulated NO release (2.0 ± 0.3 fold) was significantly reduced by 55±5 and 65±4.5% following exposure of cells to 16 and 25 mM glucose, respectively, in comparison with osmotic controls. In parallel studies, glucose inhibited both laminar shear stress and pulsatile flow-induced NO expression and release.
Hyperglycaemia impairs agonist- and flow-induced release of NO in microvascular cells. This decrease in NO production may contribute to the vascular dysfunction and impaired autoregulation in diabetic retinopathy.
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