title: Association of rat thoracic aorta dilatation by astragaloside IV with the generation of endothelium-derived hyperpolarizing factors and nitric oxide, and the blockade of Ca2+channels.
abstract: The aim of the present study was to elucidate the roles of endothelium-derived hyperpolarizing factors (EDHFs) and nitric oxide (NO) in mediating the vasodilatation response to astragaloside IV and the effects of astragaloside IV on voltage-dependent Ca2+channels and receptor-operated Ca2+channels in rat thoracic aortic rings precontracted with potassium chloride (KCl; 60 mM) or phenylephrine (PHE; 1 µM). The results showed that astragaloside IV (1×10-4-3×10-1g/l) concentration-dependently relaxed the contraction induced by KCl (10-90 mM) or PHE (1×10-9-3×10-5µM) and inhibited concentration-contraction curves for the two vasoconstrictors in the aortic rings. Preincubation with Nω-nitro-L-arginine methyl ester (L-NAME, 100 µM) significantly attenuated astragaloside IV-induced relaxation in the endothelium-intact and -denuded arterial rings precontracted with PHE. Astragaloside IV, following preincubation with L-NAME (100 µM) plus indomethacin (10 µM), exerted vasodilatation, which was depressed by tetraethtylamine (1 mM) and propargylglycine (100 µM), but not by carbenoxolone (10 µM), catalase (500 U/ml) or proadifen hydrochloride (10 µM). The action mode of astragaloside IV was evident in comparison to nifedipine. Inhibition of PHE-induced contraction by astragaloside IV (100 mg/l) was more potent compared to inhibition of KCl-induced contraction, while inhibition of KCl-induced contraction by nifedipine (100 mg/l) was more potent compared to inhibition of PHE-induced contraction by nifedipine (100 mg/l). In addition, the combination of astragaloside IV and nifedipine exhibited synergistic and additive inhibitory effects on contraction evoked by KCl, which was similar to PHE. In conclusion, astragaloside IV, as a Ca2+antagonist, relaxes the vessels through the blockade of superior receptor-operated Ca2+and inferior voltage-dependent Ca2+channels, which modulate NO from vascular endothelial cells and vascular smooth muscle cells, and EDHFs including K+and hydrogen sulfide.
authors.affiliation: Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.
authors.forename: Guanying
authors.initials: G
authors.lastname: Hu
authors.affiliation: Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.
authors.forename: Xixiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.
authors.forename: Sanyin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
keywords: Ca2+; astragaloside IV; dilatation; endothelium derived-hyperpolarizing factor; nitric oxide; thoracic aorta