ABSTRACT
Wogonin, a natural flavonoid, is one of the bioactive compounds of the medicinal herb Eucommia ulmoides OLIV. widely used in southeastern Asia for treating hypertension. However, the molecular mechanisms for the therapeutic benefits remain largely unclear. The present study investigated the vasodilatory effect of wogonin and its possible mechanisms. The flavonoid (0.1-100 µM) caused concentration-dependent relaxations in endothelium-intact aortic rings precontracted with norepinephrine (NE, 1 µM) or potassium chloride (KCl, 60 mM). Preincubation with wogonin (10, 100 µM) for 20 min significantly inhibited the contractile responses to NE (0.1, 1, 10 µM) or KCl (7.5, 15, 30, 60 mM). Relaxant responses to wogonin were not inhibited by N(G)-nitro-L-arginine methylester (100 µM) or endothelial denudation. In a Ca(2+)-free Krebs' solution, wogonin not only blocked Ca(2+) influx-dependent vasoconstriction by either NE (1 µM) or KCl (100 mM), but also inhibited NE (1 µM)-induced tonic contraction, which is dependent on intracellular Ca(2+) release. Wogonin also suppressed the elevation of [Ca(2+)]i induced by KCl (60 mM) after exhausting the calcium store in sarcoplasmic and endoplasmic reticula with thapsigargin (1 µM) or by ATP (100 µM) in primary vascular smooth muscle cells. These findings suggest that wogonin-induced responses are mainly due to the inhibition of both intracellular Ca(2+) release and extracellular Ca(2+) influx.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Eucommiaceae/chemistry , Flavanones/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Vasoconstriction/drug effects , Vasodilator Agents/pharmacology , Animals , Aorta , Calcium/metabolism , Endothelium, Vascular/metabolism , Hypertension/drug therapy , Hypertension/physiopathology , Male , Muscle, Smooth, Vascular/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Norepinephrine , Phytotherapy , Potassium Chloride , Rats, WistarABSTRACT
OBJECTIVE: To investigate the vasodilator effect and the endothelium-dependent mechanism of oroxylin A in thoracic aorta isolated from rats. METHODS: Thoracic aorta was isolated from Wistar rats. After pretreatment with norepinephrine or KCl, the effects of oroxylin A at different concentrations were detected on isolated vascular rings prepared from rats' thoracic aorta. The response of thoracic aortic ring was evaluated in the presence and absence of endothelium, and NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of nitric oxide synthase. RESULTS: Oroxylin A (10 and 100 µmol/L) caused vasodilation on endothelium-intact aortic rings pretreated with norepinephrine (1 µmol/L) and KCl (60 mmol/L) compared with the control (P<0.05, P<0.01). The vasodilation function of 10 and 100 µmol/L oroxylin A on the endothelium-denuded aorta rings was significantly lower than that on the endothelium-intact aorta rings (P<0.05, P<0.01). L-NAME pretreatment significantly attenuated the effect of 100 µmol/L oroxylin A on endothelium-intact aorta rings (P<0.05, P<0.01). CONCLUSION: Oroxylin A can induce the relaxation of the aorta ring in endothelium-dependent manner. Nitric oxide may be involved in the endothelium-dependent effect of oroxylin A.