Kaneda Takeharu, Sasaki Noriyasu, Urakawa Norimoto, Shimizu Kazumasa
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.
Pharmacology. 2016;97(3-4):171-6. doi: 10.1159/000443894. Epub 2016 Feb 3.
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 μmol/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-NG-nitroarginine methyl ester (L-NAME, 100 μmol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 μmol/l) increased cGMP contents, significantly and L-NAME (100 μmol/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.
本研究考察了二甲基亚砜（DMSO）诱导完整内皮和去内皮大鼠主动脉血管舒张的机制。DMSO（0.1 - 3%）以剂量依赖性方式抑制去氧肾上腺素（PE，1 μmol/l）诱导的收缩。然而，在无内皮的情况下，这种舒张作用较弱。在L - NG - 硝基精氨酸甲酯（L - NAME，100 μmol/l）预孵育以及去除内皮后，内皮存在时DMSO诱导的舒张增加作用减弱。在有内皮的主动脉中，DMSO（3%）和乙酰胆碱（CCh，3 μmol/l）显著增加了cGMP含量，而L - NAME（100 μmol/l）抑制了DMSO诱导的cGMP增加。在装载了fura 2的去内皮主动脉中，累积应用DMSO（1 - 3%）抑制了PE诱导的肌肉张力；然而，这种应用并未影响细胞内钙离子浓度（[Ca2+]i）水平。在PE预收缩的去内皮主动脉中，与对照组相比，在DMSO存在的情况下，对法舒地尔的舒张反应明显减弱。这些结果表明，在大鼠主动脉中，DMSO通过增加cGMP含量（与内皮细胞释放NO相关）以及部分通过抑制Rho激酶来降低收缩成分的Ca2+敏感性，从而引起血管舒张。
