Department of Pharmacology, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Environ Toxicol Pharmacol. 2010 May;29(3):290-6. doi: 10.1016/j.etap.2010.02.004. Epub 2010 Mar 11.
We hypothesized that fluoride induces vascular contraction through activation of the RhoA/Rho kinase pathway in isolated rat aortas. Rat aortic rings were mounted in organ baths and contracted with sodium fluoride (NaF). We measured the amount of GTP-RhoA as well as vascular tension. We also determined the level of phosphorylation of the myosin light chain (MLC(20)), myosin phosphatase targeting subunit 1 (MYPT1) and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17kDa (CPI17). In both physiological salt solution and Ca(2+)-free solution, NaF increased vascular tension and MLC(20) phosphorylation in dose-dependent manners. NaF increased not only phosphorylation level of MYPT1(Thr855) and CPI17(Thr38), but also the amount of GTP-RhoA. Both H1152 and Y27632, inhibitors of Rho kinase, but not Ro31-8220, an inhibitor of PKC, attenuated NaF-induced contraction and phosphorylation level of MLC(20), MYPT1(Thr855) and CPI17(Thr38). In conclusion, fluoride induces vascular contraction through activation of the RhoA/Rho kinase pathway.
我们假设氟化物通过激活分离的大鼠主动脉中的 RhoA/Rho 激酶通路诱导血管收缩。将大鼠主动脉环安装在器官浴中，并通过氟化钠（NaF）收缩。我们测量了 GTP-RhoA 的量以及血管张力。我们还测定了肌球蛋白轻链（MLC（20））、肌球蛋白磷酸酶靶向亚单位 1（MYPT1）和 PKC 增强的异三聚体 MLCP 的 17kDa 抑制蛋白（CPI17）的磷酸化水平。在生理盐溶液和无 Ca(2+)溶液中，NaF 以剂量依赖性方式增加血管张力和 MLC(20)磷酸化。NaF 不仅增加了 MYPT1(Thr855)和 CPI17(Thr38)的磷酸化水平，还增加了 GTP-RhoA 的量。Rho 激酶抑制剂 H1152 和 Y27632，但不是 PKC 抑制剂 Ro31-8220，均可减轻 NaF 诱导的收缩和 MLC(20)、MYPT1(Thr855)和 CPI17(Thr38)的磷酸化水平。总之，氟化物通过激活 RhoA/Rho 激酶通路诱导血管收缩。
