Nitric oxide (NO) scavenging and NO protecting effects of quercetin and their biological significance in vascular smooth muscle.
The flavonoid quercetin reduces blood pressure and endothelial dysfunction in animal models of hypertension. However, the results concerning the relationship between quercetin and NO present a complex picture. We have analyzed the mechanisms involved in the NO scavenging effects of quercetin and its repercussion on NO bioactivity in vascular smooth muscle. Quercetin scavenged NO with apparent zero-order kinetics with respect to NO. This effect was strongly dependent on the O(2) concentrations, so that NO decay at pH 7.4 could be fitted to the equation -d[NO]/dt = k x [O(2)] x [quercetin], where k was 0.15 M(-1) s(-1). The NO scavenger effects were prevented by superoxide dismutase (SOD), reduced by lowering pH, accompanied by O(2)(.) production and correlated with decreased NO bioactivity in rat aortic rings. However, under conditions of increased O(2)(.) concentrations, quercetin was a better scavenger of O(2)(.) than of NO. When NO scavenging by quercetin was prevented by addition of SOD, NO bioactivity was increased. Quercetin also prevented the inhibitory effects of the SOD inhibitor diethyldithiocarbamic acid (DETCA) on NO bioactivity. In the presence of DETCA, quercetin reduced tissue O(2)(.) as measured by nitro blue tetrazolium staining. In conclusion, quercetin exerts dual effects on O(2)(.) and NO. At physiological conditions of pH, O(2) concentrations and NO, quercetin effectively scavenged NO in the low micromolar range, and the rate-limiting step was the autooxidation of quercetin and the formation of O(2)(.). When the extracellular NO scavenging effect was prevented, quercetin increased the biological activity of NO, an effect related to its O(2)(.) scavenger properties and/or its inhibitory effect on tissue O(2)(.) generation.
López-López
Gustavo
G
Department of Pharmacology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain. fperez@med.ucm.es
Moreno
Laura
L
Cogolludo
Angel
A
Galisteo
Milagros
M
Ibarra
Manuel
M
Duarte
Juan
J
Lodi
Federica
F
Tamargo
Juan
J
Perez-Vizcaino
Francisco
F
D000818:Animals; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D009580:Nitroblue Tetrazolium / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*
D013481:Superoxides; D009580:Nitroblue Tetrazolium; D009569:Nitric Oxide; D011794:Quercetin; D010100:Oxygen