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 (1x10-4‑3x10‑1 g/l) concentration‑dependently relaxed the contraction induced by KCl (10‑90 mM) or PHE (1x10‑9‑3x10‑5 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.