Fluoride induces vascular contraction through activation of RhoA/Rho kinase pathway in isolated rat aortas

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 (MLC20), myosin phosphatase targeting subunit 1 (MYPT1) and PKC-potentiated inhibitory protein for heterotrimeric MLCP of 17 kDa (CPI17). In both physiological salt solution and Ca2+-free solution, NaF increased vascular tension and MLC20 phosphorylation in dose-dependent manners. NaF increased not only phosphorylation level of MYPT1Thr855 and CPI17Thr38, 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 MLC20, MYPT1Thr855 and CPI17Thr38. In conclusion, fluoride induces vascular contraction through activation of the RhoA/Rho kinase pathway.