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


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.


RESULTS
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).


CONCLUSIONS
DiOHF, acutely in vitro or after 1 week treatment in vivo, reduces oxidant stress and preserves endothelium-dependent relaxation in aortae from diabetic rats.
Woodman
Owen L
OL
School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia. owen.woodman@rmit.edu.au
Malakul
Wachirawadee
W
D000166:Acridines; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D003925:Diabetic Angiopathies / Q000473:pathology / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D044948:Flavonols / Q000494:pharmacology*; D066298:In Vitro Techniques; D049449:Luminescence; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000166:Acridines; D001786:Blood Glucose; D044948:Flavonols; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; C529890:3',4'-dihydroxyflavonol