Vasodilatory effects of flavonoids in rat aortic smooth muscle. Structure-activity relationships.
1. Flavonoids relaxed the contractions induced by noradrenaline, KCl or phorbol 12-myristate, 13-acetate in rat aortic strips, the order of potency being: flavonols (quercetin, kaempferol, pentamethylquercetin) > flavones(luteolin, apigenin) > flavanols((+)-catechin, (-)-epicatechin) which correlates with the reported order of potency to inhibit protein kinase C. 2. The relaxant effects of kaempferol and luteolin were slightly potentiated by isoprenaline and those of pentamethylquercetin, kaempferol and apigenin by sodium nitroprusside. 3. It is concluded that the main vasodilatory mechanism of flavonoids seems to be the inhibition of protein kinase C. Inhibition of cyclic nucleotide phosphodiesterases or decreased Ca2+ uptake may also contribute to their vasodilatory effects.
Duarte
J
J
Department of Pharmacology, School of Pharmacy, Universidad de Granada, Spain.
Pérez Vizcaíno
F
F
Utrilla
P
P
Jiménez
J
J
Tamargo
J
J
Zarzuelo
A
A
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D005419:Flavonoids; D014665:Vasodilator Agents; D009599:Nitroprusside; D011189:Potassium Chloride; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine