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

Chen, Yulong; Xu, Cang-Bao LU ; Wei, Yahui; Zhang, Yaping and Cao, Ailan (2016) In Experimental and Therapeutic Medicine 12(4). p.2241-2246
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,... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ca influx, K channel, Nitric oxide, Resveratrol, Superior mesenteric artery, Vasorelaxant effects
in
Experimental and Therapeutic Medicine
volume
12
issue
4
pages
6 pages
publisher
Spandidos Publications Ltd
external identifiers
  • scopus:84987942266
  • wos:000385578200044
ISSN
1792-0981
DOI
10.3892/etm.2016.3605
language
English
LU publication?
yes
id
c42c19f0-432e-4d4b-bb0e-8f5abfa1c550
date added to LUP
2016-10-03 14:28:20
date last changed
2017-11-12 04:24:49
@article{c42c19f0-432e-4d4b-bb0e-8f5abfa1c550,
  abstract     = {<p>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 (E<sub>max</sub>, 97.66±0.79%; pD<sub>2</sub>, 4.30±0.14) or KCl (E<sub>max</sub>, 101.3±0.6%; pD<sub>2</sub>, 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. N<sup>G</sup>-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 Ca<sup>2+</sup>-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<sup>+</sup> channels and ATP-sensitive K<sup>+</sup> channels and blockade of extracellular Ca<sup>2+</sup> influx.</p>},
  author       = {Chen, Yulong and Xu, Cang-Bao and Wei, Yahui and Zhang, Yaping and Cao, Ailan},
  issn         = {1792-0981},
  keyword      = {Ca influx,K channel,Nitric oxide,Resveratrol,Superior mesenteric artery,Vasorelaxant effects},
  language     = {eng},
  month        = {10},
  number       = {4},
  pages        = {2241--2246},
  publisher    = {Spandidos Publications Ltd},
  series       = {Experimental and Therapeutic Medicine},
  title        = {Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries},
  url          = {http://dx.doi.org/10.3892/etm.2016.3605},
  volume       = {12},
  year         = {2016},
}