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

Hu,Guanying; Li,Xixiong; Zhang,Sanyin; Wang,Xin

doi:10.3892/br.2016.680

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

Authors:
- Guanying Hu
- Xixiong Li
- Sanyin Zhang
- Xin Wang
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Affiliations: Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China
Published online on: May 18, 2016 https://doi.org/10.3892/br.2016.680
Pages: 27-34
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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1	Dong HY, Yang JG, Xiao ZQ, Feng WY, Deng X, Zhang LT and Wei YX: Pro-angiogenic effects of four Chinese medicines and three herbal prescription in chicken chorioallantoic membrane model. Zhong Yao Cai. 36:1297–1300. 2013.(In Chinese). PubMed/NCBI
2	Ji KT, Tang JF and Chai JD: Effect of astragaloside against the oxidative damage on endothelial cells. Zhongguo Zhong Xi Yi Jie He Za Zhi. 31:807–810. 2011.(In Chinese). PubMed/NCBI
3	Qiu YY, Zhu JX, Bian T, Gao F, Qian XF, Du Q, Yuan MY, Sun H, Shi LZ and Yu MH: Protective effects of astragaloside IV against ovalbumin-induced lung inflammation are regulated/mediated by T-bet/GATA-3. Pharmacology. 94:51–59. 2014. View Article : Google Scholar : PubMed/NCBI
4	Cheng X, Gu J, Zhang M, Yuan J, Zhao B, Jiang J and Jia X: Astragaloside IV inhibits migration and invasion in human lung cancer A549 cells via regulating PKC-α-ERK1/2-NF-κB pathway. Int Immunopharmacol. 23:304–313. 2014. View Article : Google Scholar : PubMed/NCBI
5	Qi Q, Mao Y, Yi J, Li D, Zhu K and Cha X: Anti-fibrotic effects of Astragaloside IV in systemic sclerosis. Cell Physiol Biochem. 34:2105–2116. 2014. View Article : Google Scholar : PubMed/NCBI
6	Shang L, Qu Z, Sun L, Wang Y, Liu F, Wang S, Gao H and Jiang F: Astragaloside IV inhibits adenovirus replication and apoptosis in A549 cells in vitro. J Pharm Pharmacol. 63:688–694. 2011. View Article : Google Scholar : PubMed/NCBI
7	Li YR, Cao W, Guo J, Miao S, Ding GR, Li KC, Wang J and Guo GZ: Comparative investigations on the protective effects of rhodioside, ciwujianoside-B and astragaloside IV on radiation injuries of the hematopoietic system in mice. Phytother Res. 25:644–653. 2011. View Article : Google Scholar : PubMed/NCBI
8	Shan YH, Peng LH, Liu X, Chen X, Xiong J and Gao JQ: Silk fibroin/gelatin electrospun nanofibrous dressing functionalized with astragaloside IV induces healing and anti-scar effects on burn wound. Int J Pharm. 479:291–301. 2015. View Article : Google Scholar : PubMed/NCBI
9	Wang SG, Xu Y, Chen JD, Yang CH and Chen XH: Astragaloside IV stimulates angiogenesis and increases nitric oxide accumulation via JAK2/STAT3 and ERK1/2 pathway. Molecules. 18:12809–12819. 2013. View Article : Google Scholar : PubMed/NCBI
10	Yang QY, Lu S and Sun HR: Effects of astragalus on cardiac function and serum tumor necrosis factor-alpha level in patients with chronic heart failure. Zhongguo Zhong Xi Yi Jie He Za Zhi. 30:699–701. 2010.(In Chinese). PubMed/NCBI
11	Liu KZ, Li JB, Lu HL, Wen JK and Han M: Effects of Astragalus and saponins of Panax notoginseng on MMP-9 in patients with type 2 diabetic macroangiopathy. Zhongguo Zhong Yao Za Zhi. 29:264–266. 2004.(In Chinese). PubMed/NCBI
12	Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano K, Harada K, Miyamoto S, Nakazawa H, Won KJ and Sato K: Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev. 49:157–230. 1997.PubMed/NCBI
13	Taggart MJ, Menice CB, Morgan KG and Wray S: Effect of metabolic inhibition on intracellular Ca²⁺, phosphorylation of myosin regulatory light chain and force in rat smooth muscle. J Physiol. 499:485–496. 1997. View Article : Google Scholar : PubMed/NCBI
14	Bełtowski J and Jamroz-Wiśniewska A: Hydrogen sulfide and endothelium-dependent vasorelaxation. Molecules. 19:21183–21199. 2014. View Article : Google Scholar : PubMed/NCBI
15	Jobe SO, Ramadoss J, Wargin AJ and Magness RR: Estradiol-17β and its cytochrome P450- and catechol-O-methyltransferase-derived metabolites selectively stimulate production of prostacyclin in uterine artery endothelial cells: Role of estrogen receptor-α versus estrogen receptor-β. Hypertension. 61:509–518. 2013. View Article : Google Scholar : PubMed/NCBI
16	Mathewson AM and Dunn WR: A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries. PLoS One. 9:e1119772014. View Article : Google Scholar : PubMed/NCBI
17	Xavier FE, Blanco-Rivero J, Sastre E, Caracuel L, Callejo M and Balfagón G: Tranilast increases vasodilator response to acetylcholine in rat mesenteric resistance arteries through increased EDHF participation. PLoS One. 9:e1003562014. View Article : Google Scholar : PubMed/NCBI
18	Wang QH, Zhu L and Chen H: Effect of astragaloside IV on thoracic aortic rings isolated from fat. Chin Pharmacol Bull. 22:1319–1323. 2006.
19	Zhang C, Wang XH, Zhong MF, Liu RH, Li HL, Zhang WD and Chen H: Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic rings. Clin Exp Pharmacol Physiol. 34:387–392. 2007. View Article : Google Scholar : PubMed/NCBI
20	Zhang WD, Zhang C, Wang XH, Gao PJ, Zhu DL, Chen H, Liu RH and Li HL: Astragaloside IV dilates aortic vessels from normal and spontaneously hypertensive rats through endothelium-dependent and endothelium-independent ways. Planta Med. 72:621–626. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wang KH: Aqueous extracts from Chinese herb Ginseng, Astragalus membranaceus and Scutellaria baicalensis increase the expression both NO and cGMP. Foreign Med Sci. 18:38–39. 1996.
22	Hamada H, Damron DS, Hong SJ, Van Wagoner DR and Murray PA: Phenylephrine-induced Ca²⁺ oscillations in canine pulmonary artery smooth muscle cells. Circ Res. 81:812–823. 1997. View Article : Google Scholar : PubMed/NCBI
23	Su X, Smolock EM, Marcel KN and Moreland RS: Phosphatidylinositol 3-kinase modulates vascular smooth muscle contraction by calcium and myosin light chain phosphorylation-independent and -dependent pathways. Am J Physiol Heart Circ Physiol. 286:H657–H666. 2004. View Article : Google Scholar : PubMed/NCBI
24	Carmignoto G, Pasti L and Pozzan T: On the role of voltage-dependent calcium channels in calcium signaling of astrocytes in situ. J Neurosci. 18:4637–4645. 1998.PubMed/NCBI
25	Ratz PH and Berg KM: 2-Aminoethoxydiphenyl borate inhibits KCl-induced vascular smooth muscle contraction. Eur J Pharmacol. 541:177–183. 2006. View Article : Google Scholar : PubMed/NCBI
26	Kravtsov GM and Kwan CY: A revisitation on the mechanism of action of KCl-induced vascular smooth muscle contraction: A key role of cation binding to the plasma membrane. Biol Signals. 4:160–167. 1995. View Article : Google Scholar : PubMed/NCBI
27	Lee CH, Poburko D, Sahota P, Sandhu J, Ruehlmann DO and van Breemen C: The mechanism of phenylephrine-mediated [Ca(2+)](i) oscillations underlying tonic contraction in the rabbit inferior vena cava. J Physiol. 534:641–650. 2001. View Article : Google Scholar : PubMed/NCBI
28	Hirata S, Enoki T, Kitamura R, Vinh VH, Nakamura K and Mori K: Effects of isoflurane on receptor-operated Ca²⁺ channels in rat aortic smooth muscle. Br J Anaesth. 81:578–583. 1998. View Article : Google Scholar : PubMed/NCBI
29	Sensch O, Vierling W, Brandt W and Reiter M: Effects of inhibition of calcium and potassium currents in guinea-pig cardiac contraction: Comparison of beta-caryophyllene oxide, eugenol, and nifedipine. Br J Pharmacol. 131:1089–1096. 2000. View Article : Google Scholar : PubMed/NCBI
30	Muraki K, Bolton TB, Imaizumi Y and Watanabe M: Effect of isoprenaline on Ca²⁺ channel current in single smooth muscle cells isolated from taenia of the guinea-pig caecum. J Physiol. 471:563–582. 1993. View Article : Google Scholar : PubMed/NCBI
31	Denis MC, Furtos A, Dudonné S, Montoudis A, Garofalo C, Desjardins Y, Delvin E and Levy E: Apple peel polyphenols and their beneficial actions on oxidative stress and inflammation. PLoS One. 8:e537252013. View Article : Google Scholar : PubMed/NCBI
32	Zhang M, Sun S, Tang N, Cai W and Qian L: Oral administration of alkylglycerols differentially modulates high-fat diet-induced obesity and insulin resistance in mice. Evid Based Complement Alternat Med. 2013:8340272013. View Article : Google Scholar : PubMed/NCBI
33	Bak MJ, Hong SG, Lee JW and Jeong WS: Red ginseng marc oil inhibits iNOS and COX-2 via NFκB and p38 pathways in LPS-stimulated RAW 264.7 macrophages. Molecules. 17:13769–13786. 2012. View Article : Google Scholar : PubMed/NCBI
34	Ayele Y, Kim JA, Park E, Kim YJ, Retta N, Dessie G, Rhee SK, Koh K, Nam KW and Kim HS: A methanol extract of Adansonia digitata L. leaves inhibits pro-inflammatory iNOS possibly via the inhibition of NF-κB activation. Biomol Ther (Seoul). 21:146–152. 2013. View Article : Google Scholar : PubMed/NCBI
35	Campbell WB and Gauthier KM: Inducible endothelium-derived hyperpolarizing factor: Role of the 15-lipoxygenase-EDHF pathway. J Cardiovasc Pharmacol. 61:176–187. 2013. View Article : Google Scholar : PubMed/NCBI
36	Garry A, Edwards DH, Fallis IF, Jenkins RL and Griffith TM: Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by generating hydrogen peroxide. Cardiovasc Res. 84:218–226. 2009. View Article : Google Scholar : PubMed/NCBI
37	Jamroz-Wiśniewska A, Gertler A, Solomon G, Wood ME, Whiteman M and Bełtowski J: Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: Role of nitric oxide and hydrogen sulfide. PLoS One. 9:e867442014. View Article : Google Scholar : PubMed/NCBI
38	Fujiwara H, Wake Y, Hashikawa-Hobara N, Makino K, Takatori S, Zamami Y, Kitamura Y and Kawasaki H: Endothelium-derived relaxing factor-mediated vasodilation in mouse mesenteric vascular beds. J Pharmacol Sci. 118:373–381. 2012. View Article : Google Scholar : PubMed/NCBI