Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta

Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta
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DOI:
10.1159/000443894
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发表时间:
2016-01-01
期刊:
影响因子:
3.1
通讯作者:
Shimizu, Kazumasa
Shimizu, Kazumasa
中科院分区:
医学4区
文献类型:
--
作者:
Kaneda, Takeharu;Sasaki, Noriyasu;Shimizu, Kazumasa

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本研究探讨了二甲基亚砜(DMSO)对内皮完整和去内皮大鼠主动脉舒缩作用的机制。二甲基亚砜(0.1-3%)可剂量依赖性地抑制苯肾上腺素(PE,1mU/L)引起的收缩。然而,在没有内皮的情况下,这种松弛程度较低。用L-N-G-硝基精氨酸甲酯(L-NAME,100Mol/L)预孵育和去除内皮可减弱二甲基亚砜引起的内皮松弛增加。在有内皮的主动脉中,二甲基亚砜(3%)和CCH(3mU/L)可显著增加cGMP的含量,而L-NAME(100mU/L)可抑制二甲基亚砜引起的cGMP增加。在Fura-2负载的去内皮主动脉上,累积应用DMSO(1-3%)可抑制PE诱导的肌张力,但不影响[Ca~(2+)](I)水平。在PE预收缩的内皮剥脱的主动脉中,在DMSO存在的情况下,法舒地尔的松弛反应明显低于对照组。这些结果提示,DMSO通过增加血管内皮细胞释放NO相关的cGMP含量,降低收缩元件对钙离子的敏感性,部分通过抑制Rho-K来起到松弛作用。(C)2016年S.Karger AG,巴塞尔
This study examined the mechanism of vasorelaxation induced by dimethyl sulfoxide (DMSO) in endothelium-intact and -denuded rat aorta. DMSO (0.1-3%) inhibited phenylephrine (PE, 1 mu mol/l)-induced contraction in a dose-dependent manner. However, this relaxation was lower in the absence of the endothelium. Increase in DMSO-induced relaxation in the presence of the endothelium was attenuated by preincubation in L-N-G-nitroarginine methyl ester (L-NAME, 100 mu mol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 mu mol/l) increased cGMP contents, significantly and L-NAME (100 mu mol/l) inhibited the DMSO-induced increases of cGMP. In fura 2-loaded endothelium-denuded aorta, cumulative application of DMSO (1-3%) inhibited PE-induced muscle tension; however, this application did not affect the [Ca2+](i) level. In PE-precontracted endothelium-denuded aorta, relaxation responses to fasudil were significantly less in the presence of DMSO compared to the control. These results suggest that DMSO causes relaxation by increasing the cGMP content in correlation with the release of NO from endothelial cells and by decreasing the Ca2+ sensitivity of contractile elements partly via inhibiting Rho-kinase in rat aorta. (C) 2016 S. Karger AG, Basel