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

• Published in: Biomedical reports Vol. 5; no. 1; pp. 27 - 34
• Main Authors: HU, GUANYING, LI, XIXIONG, ZHANG, SANYIN, WANG, XIN
• Format: Journal Article
• Language: English
• Published: Athens D.A. Spandidos 01.07.2016; Spandidos Publications UK Ltd
• Subjects: Aorta; Arginine; astragaloside IV; Blood vessels; Ca2; Calcium channels; Calcium channels (voltage-gated); Catalase; Channels; Chinese medicine; Coronary vessels; dilatation; Electric potential; Endothelial cells; Endothelium; endothelium derived-hyperpolarizing factor; Hydrogen sulfide; Indomethacin; Medical research; NG-Nitroarginine methyl ester; Nifedipine; Nitric oxide; Phenylephrine; Potassium; Potassium chloride; Rodents; Smooth muscle; Studies; Sulfide; thoracic aorta; Thorax; Vasoconstrictors; Vasodilation; Veins & arteries; China
• ISSN: 2049-9434; 2049-9442
• DOI: 10.3892/br.2016.680

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 (1×10−4-3×10−1 g/l) concentration-dependently relaxed the contraction induced by KCl (10-90 mM) or PHE (1×10−9-3×10−5 µM) 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.