Nakaike R, Shimokawa H, Owada M K, Tokunaga O, Yasutake H, Kishimoto T, Imada C, Shiraishi T, Egashira K, Takeshita A
Research Institute of Angiocardiology, Kyushu University School of Medicine, Fukuoka, Japan.
Am J Physiol. 1996 Jul;271(1 Pt 2):H296-302. doi: 10.1152/ajpheart.1996.271.1.H296.
The effects of sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, on the endothelial nitric oxide (NO) pathway were studied in vitro. Vanadate caused endothelium-dependent relaxations in isolated porcine coronary arteries, which were abolished by N omega-nitro-L-arginine methyl ester. The relaxations were also abolished by pertussis toxin, an inhibitor of certain G proteins. Tyrosine kinase inhibitors, genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenyl-methylcinnamamide (ST-638), significantly attenuated the vanadate-induced relaxations. Vanadate also caused pertussis toxin-sensitive, endothelium-dependent relaxations in isolated porcine renal and femoral arteries and jugular veins. Immunoblots, using an antibody to phosphotyrosines and to c-Src in native porcine aortic endothelial cells, respectively, showed that vanadate induced an elevation of phosphotyrosine proteins and a decrease in the amount of the active form of c-Src family kinases; both changes were markedly suppressed by cotreatment with ST-638. These results indicate that in porcine blood vessels, vanadate causes a synthesis of endothelium-derived NO for which endothelial tyrosine kinases and pertussis toxin-sensitive G protein are considered to be closely involved.
在体外研究了蛋白酪氨酸磷酸酶抑制剂原钒酸钠对内皮型一氧化氮（NO）途径的影响。钒酸盐可引起离体猪冠状动脉的内皮依赖性舒张，而Nω-硝基-L-精氨酸甲酯可消除这种舒张作用。百日咳毒素（一种某些G蛋白的抑制剂）也可消除这种舒张作用。酪氨酸激酶抑制剂染料木黄酮和α-氰基-3-乙氧基-4-羟基-5-苯基甲基肉桂酰胺（ST-638）可显著减弱钒酸盐诱导的舒张作用。钒酸盐还可引起离体猪肾动脉、股动脉和颈静脉的百日咳毒素敏感的内皮依赖性舒张。分别使用针对磷酸酪氨酸和天然猪主动脉内皮细胞中c-Src的抗体进行免疫印迹分析表明，钒酸盐可诱导磷酸酪氨酸蛋白升高以及c-Src家族激酶活性形式的量减少；与ST-638共同处理可显著抑制这两种变化。这些结果表明，在猪血管中，钒酸盐可导致内皮源性NO的合成，内皮酪氨酸激酶和百日咳毒素敏感的G蛋白被认为密切参与其中。
