Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

Chen,Yulong; Xu,Cangbao; Wei,Yahui; Zhang,Yaping; Cao,Ailan

doi:10.3892/etm.2016.3605

Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

Authors:
- Yulong Chen
- Cangbao Xu
- Yahui Wei
- Yaping Zhang
- Ailan Cao
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Affiliations: Shaanxi Pharmaceutical Development Center, Shaanxi Pharmaceutical Holding Group Co., Ltd., Xi'an, Shaanxi 710075, P.R. China, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China, Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, P.R. China
Published online on: August 22, 2016 https://doi.org/10.3892/etm.2016.3605
Pages: 2241-2246

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Abstract

Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration‑dependently relaxed endothelium‑intact superior mesenteric artery rings pre‑contracted by phenylephrine hydrochloride (Emax, 97.66±0.79%; pD2, 4.30±0.14) or KCl (Emax, 101.3±0.6%; pD2, 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. NG-nitro-L‑arginine methyl ester (100 µM) significantly inhibited the Res‑induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3‑a] quinoxalin‑1‑one (10 µM) and indomethacin (5 µM) each had no effect on the Res‑induced vasorelaxation. In artery rings without endothelium, the vasorelaxation induced by Res was attenuated by 4‑aminopyridine (100 µM) and glibenclamide (10 µM). However, barium chloride dehydrate (10 µM) and tetraethylammonium chloride (1 mM) did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited the contraction induced by an increase in external calcium concentration in Ca2+‑free medium plus KCl (60 mM). These results suggest that Res induces relaxation in superior mesenteric arterial rings through an endothelium‑dependent pathway, involving nitric oxide release, and also through an endothelium‑independent pathway, with opening of voltage‑dependent K+ channels and ATP‑sensitive K+ channels and blockade of extracellular Ca2+ influx.

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1	Koo SH and Montminy M: In vino veritas: A tale of two sirt1s? Cell. 127:1091–1093. 2006. View Article : Google Scholar : PubMed/NCBI
2	Wang H, Yang YJ, Qian HY, Zhang Q, Xu H and Li JJ: Resveratrol in cardiovascular disease: What is known from current research? Heart Fail Rev. 17:437–448. 2012. View Article : Google Scholar : PubMed/NCBI
3	Naderali EK, Doyle PJ and Williams G: Resveratrol induces vasorelaxation of mesenteric and uterine arteries from female guinea-pigs. Clin Sci (Lond). 98:537–543. 2000. View Article : Google Scholar : PubMed/NCBI
4	Soylemez S, Gurdal H, Sepici A and Akar F: The effect of long-term resveratrol treatment on relaxation to estrogen in aortae from male and female rats: Role of nitric oxide and superoxide. Vascul Pharmacol. 49:97–105. 2008. View Article : Google Scholar : PubMed/NCBI
5	Taguchi K, Hida M, Matsumoto T and Kobayashi T: Resveratrol ameliorates clonidine-induced endothelium-dependent relaxation involving Akt and endothelial nitric oxide synthase regulation in type 2 diabetic mice. Biol Pharm Bull. 38:1864–1872. 2015. View Article : Google Scholar : PubMed/NCBI
6	Novakovic A, Bukarica LG, Kanjuh V and Heinle H: Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol. Basic Clin Pharmacol Toxicol. 99:360–364. 2006. View Article : Google Scholar : PubMed/NCBI
7	Shen M, Zhao L, Wu RX, Yue SQ and Pei JM: The vasorelaxing effect of resveratrol on abdominal aorta from rats and its underlying mechanisms. Vascul Pharmacol. 58:64–70. 2013. View Article : Google Scholar : PubMed/NCBI
8	Zhang HY, Xu CQ, Li HZ, Li BX, Zhang YQ and Zhang YN: Effects of resveratrol on isolated thoracic aorta rings of rats. Zhongguo Zhong Yao Za Zhi. 30:1283–1286. 2005.(In Chinese). PubMed/NCBI
9	Novakovic A, Gojkovic-Bukarica L, Peric M, Nezic D, Djukanovic B, Markovic-Lipkovski J and Heinle H: The mechanism of endothelium-independent relaxation induced by the wine polyphenol resveratrol in human internal mammary artery. J Pharmacol Sci. 101:85–90. 2006. View Article : Google Scholar : PubMed/NCBI
10	Gojkovic-Bukarica L, Novakovic A, Kanjuh V, Bumbasirevic M, Lesic A and Heinle H: A role of ion channels in the endothelium-independent relaxation of rat mesenteric artery induced by resveratrol. J Pharmacol Sci. 108:124–130. 2008. View Article : Google Scholar : PubMed/NCBI
11	Naderali EK, Smith SL, Doyle PJ and Williams G: The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean andobese rats. Clin Sci (Lond). 100:55–60. 2001. View Article : Google Scholar : PubMed/NCBI
12	Li HF, Tian ZF, Qiu XQ, Wu JX, Zhang P and Jia ZJ: A study of mechanisms involved in vasodilatation induced by resveratrol in isolated porcine coronary artery. Physiol Res. 55:365–372. 2006.PubMed/NCBI
13	Mathiassen ON, Buus NH, Sihm I, Thybo NK, Mørn B, Schroeder AP, Thygesen K, Aalkjaer C, Lederballe O, Mulvany MJ and Christensen KL: Small artery structure is an independent predictor of cardiovascular events in essential hypertension. J Hypertens. 25:1021–1026. 2007. View Article : Google Scholar : PubMed/NCBI
14	Cao YX, Zhang W, He JY, He LC and Xu CB: Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca²⁺influx and release. Vascul Pharmacol. 45:171–176. 2006. View Article : Google Scholar : PubMed/NCBI
15	Zhu XM, Fang LH, Li YJ and Du GH: Endothelium-dependent and -independent relaxation induced by pinocembrin in rat aortic rings. Vascul Pharmacol. 46:160–165. 2007. View Article : Google Scholar : PubMed/NCBI
16	Rubanyi GM: The role of endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol. 22:(Suppl 4). S1–S14. 1993. View Article : Google Scholar : PubMed/NCBI
17	Nelson MT and Quayle JM: Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 268:C799–C822. 1995.PubMed/NCBI
18	Bolotina VM, Najibi S, Palacino JJ, Pagano PJ and Cohen RA: Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature. 368:850–853. 1994. View Article : Google Scholar : PubMed/NCBI
19	Jackson WF: Potassium channelsin the peripheral microcirculation. Microcirculation. 12:113–127. 2005. View Article : Google Scholar : PubMed/NCBI
20	Brayden JE: Potassium channels in vascular smooth muscle. Clin Exp Pharmacol Physiol. 23:1069–1076. 1996. View Article : Google Scholar : PubMed/NCBI
21	Vergara C, Latorre R, Marrion NV and Adelman JP: Calcium-activated potassium channels. Curr Opin Neurobiol. 8:321–329. 1998. View Article : Google Scholar : PubMed/NCBI
22	Horowitz A, Menice CB, Laporte R and Morgan KG: Mechanisms of smooth muscle contraction. Physiol Rev. 76:967–1003. 1996.PubMed/NCBI
23	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
24	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
25	Lee CN, Wong KL, Liu JC, Chen YJ, Cheng JT and Chan P: Inhibitory effect of stevioside on calcium influx to produce antihypertension. Planta Med. 67:796–799. 2001. View Article : Google Scholar : PubMed/NCBI
26	Tanaka Y and Tashjian AH Jr: Thimerosal potentiates Ca2+ release mediated by both the inositol 1,4,5-trisphosphate and the ryanodine receptors in sea urchin eggs. Implications for mechanistic studies on Ca²⁺ signaling. J Biol Chem. 269:11247–11253. 1994.PubMed/NCBI
27	Eckert RE, Karsten AJ, Utz J and Ziegler M: Regulation of renal artery smooth muscle tone by alpha1-adrenoceptors: Role of voltage-gated calcium channels and intracellular calcium stores. Urol Res. 28:122–127. 2000. View Article : Google Scholar : PubMed/NCBI