3',4'-Dihydroxyflavonol prevents diabetes-induced endothelial dysfunction in rat aorta

Aims: Diabetes increases oxidant stress and impairs endothelium-dependent relaxation. We investigated whether the antioxidant 3′,4′-dihydroxyflavonol (DiOHF) reduces the release of superoxide (O2−) and preserves endothelial function in aortae from diabetic rats. Main methods: Type-1 diabetes was induced in Sprague–Dawley rats by streptozotocin (STZ) treatment (55 mg/kg i.v.) and vascular reactivity and superoxide generation were assessed in aortic rings using standard organ bath techniques and lucigenin-enhanced chemiluminescence respectively. Key findings: Eight weeks after STZ treatment blood glucose was elevated (39.4 ± 0.4 mM) compared to citrate treated control rats (5.5 ± 0.1 mM, P < 0.05) and there was an increased aortic generation of O2− (control 670 ± 101, diabetic 1535 ± 249 units/mg dry weight, P < 0.05). In aortic rings acetylcholine (ACh)-induced relaxation was impaired (Rmax control 78 ± 2, diabetic 66 ± 3%, P < 0.01) whereas endothelium-independent relaxation to sodium nitroprusside (SNP) was unaffected (Rmax control 100 ± 1, diabetic 101 ± 2%). When aortic rings were acutely exposed to DiOHF (10− 5 M) there was a significant reduction in the detection of O2− (control 124 ± 15, diabetic 165 ± 21 units/mg, P < 0.01) and enhanced relaxation to ACh (Rmax control 84 ± 3, diabetic 87 ± 3%). Two separate groups of rats (control and diabetic) were treated daily with DiOHF (5 mg/kg i.p.) for 7 days. DiOHF treatment reduced superoxide generation in diabetic aortae (untreated diabetic 1471 ± 358, DiOHF-treated diabetic 580 ± 115 units/mg, P < 0.05) and enhanced acetylcholine-induced relaxation (Rmax untreated diabetic 58 ± 5, DiOHF-treated diabetic 71 ± 4%, P < 0.05). Significance: DiOHF, acutely in vitro or after 1 week treatment in vivo, reduces oxidant stress and preserves endothelium-dependent relaxation in aortae from diabetic rats