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N Horio, AC Clermont, BD Shoelson, T Abiko, EP Feener, SE Bursell; Impaired Endothelium-Dependent Vasodilatory Response in Diabetic Rats Is Ameliorated with Angiotensin Type 1 Receptor Blockade using Candesartan . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1333.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Diabetes associated endothelial dysfunction plays an important role in progression of vascular complications, including diabetic retinopathy. Here, we first determined whether acetylcholine (ACh)-induced endothelium-dependent vasodilation is impaired in streptozotocin (STZ)-induced diabetic rats, and then investigated whether candesartan, an angiotensin type 1 (AT1) receptor blocker (ARB) can affect this endothelium-dependent vasodilatory response. Methods:Retinal blood flow (RBF) responses to intravitreally injected ACh (10-6 to 10-3 M) were measured with our video fluorescein angiography methodology in non-diabetic and diabetic rats. Diabetic rats after 1-week diabetes were treated with candesartan (10 µg/ml in drinking water) for a further 1-week period. Results:In non-diabetic rats, ACh induced a rapid, dose-dependent transient increase in RBF and retinal vessel diameters (maximal response 2 min after injection and a return to the baseline by 10 min). 10-4 M ACh induced the maximal RBF response (960.1±165.6 vs 589.6±135.3 pixel2/sec baseline, P<0.01). In diabetic rats, the ACh-induced RBF responses were significantly attenuated (P<0.05). Control diabetic rats in the candesartan treatment study showed comparable attenuated 10-5 M ACh-induced % changes in RBF response (11.5±24.5% diabetic vs 52.7±17.7% non-diabetic, P<0.01). Candesartan treated diabetic rats had an increased ACh-induced %RBF change (53.2±37.6%, P<0.05 compared with untreated diabetic rats), which was comparable to untreated non-diabetic rats. Vein diameters also showed vasodilation in treated diabetic rats (11.5±7.8% treatment vs 2.2±2.5% control, P<0.05). Conclusion:These findings provide the first demonstration of impaired retinal endothelium-dependent vasodilation in type 1diabetes. Inhibition of the renin-angiotensin system using an ARB ameliorates this retinal dysfunction in diabetes.
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