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

Abstract

AIMS Diabetes increases oxidant stress and impairs endothelium-dependent relaxation. We investigated whether the antioxidant 3',4'-dihydroxyflavonol (DiOHF) reduces the release of superoxide (O(2)(-)) 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 O(2)(-) (control 670+/-101, diabetic 1535+/-249 units/mg dry weight, P<0.05). In aortic rings acetylcholine (ACh)-induced relaxation was impaired (R(max) control 78+/-2, diabetic 66+/-3%, P<0.01) whereas endothelium-independent relaxation to sodium nitroprusside (SNP) was unaffected (R(max) 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 O(2)(-) (control 124+/-15, diabetic 165+/-21 units/mg, P<0.01) and enhanced relaxation to ACh (R(max) 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 (R(max) 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.

DOI: 10.1016/j.lfs.2009.04.012
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@article{Woodman200934DihydroxyflavonolPD, title={3',4'-Dihydroxyflavonol prevents diabetes-induced endothelial dysfunction in rat aorta.}, author={Owen L. Woodman and Wachirawadee Malakul}, journal={Life sciences}, year={2009}, volume={85 1-2}, pages={54-9} }