3', 4'-dihydroxyflavonol enhances nitric oxide bioavailability and improves vascular function after ischemia and reperfusion injury in the rat.
We hypothesized that 3',4'-dihydroxyflavonol (DiOHF) by scavenging superoxide anions (O2-*) would increase the bioavailability of NO and potentiate NO-mediated relaxation in the rat aorta. Furthermore we hypothesized that DiOHF, by its antioxidant activity, would preserve responses to acetylcholine (ACh) in the presence of O2-* generators in the aorta in vitro and after ischemia and reperfusion of the rat hindquarters vasculature in situ. Using lucigenin-enhanced chemiluminescence we demonstrated that DiOHF caused a concentration-dependent reduction in O2-* accumulation whether generated by xanthine/xanthine oxidase in a cell-free system or by rat isolated aorta in the presence of NADPH. DiOHF also prevented the inhibitory effects of xanthine/xanthine oxidase and pyrogallol on vasorelaxation to ACh and sodium nitroprusside (SNP) in the rat aorta in vitro, and attenuated the vascular dysfunction caused by 2 h ischemia and 2 h reperfusion (I/R) in the rat hindquarters. I/R significantly reduced the dilator responses to both ACh and SNP; however, this effect was attenuated when DiOHF was given before the onset of ischemia or reperfusion. In conclusion, DiOHF, by scavenging O2-*, increases the relaxant activity of ACh and SNP and reduces the degree of inhibition of xanthine/xanthine oxidase or pyrogallol on the response to ACh. DiOHF reduces the adverse effects of I/R on vascular function by increasing NO bioavailability suggesting that it may be useful in preventing reperfusion injury.
Chan
Elsa C H
EC
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Drummond
Grant R
GR
Woodman
Owen L
OL
D000110:Acetylcholinesterase / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D004347:Drug Interactions; D044948:Flavonols / Q000627:therapeutic use*; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D044948:Flavonols; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase