Furthermore, several reports have suggested that lead exposure increases the expression of iNOS in aorta (Vaziri et al., 1999a, Vaziri et al., 1999b, Vaziri et al., 2001 and Fiorim et al., 2011), heart (Vaziri et al., 2001) and kidney (Gonick et al., 1997 and Vaziri

et al., 2001). NO produces vasodilation of the vascular smooth muscle cells in all types of blood vessels, especially in conductance arteries. Moreover, NO could also stimulate Na+/K+-ATPase activity (Gupta et al., 1994) and open K+ channels (Bolotina et al., 1994, Félétou and Vanhoutte, 2006 and Félétou and Vanhoutte, 2009), which contribute to reduced vascular tone. The activation of Na+/K+-ATPase activity is an important mechanism contributing Ku-0059436 molecular weight to the maintenance Epacadostat mouse of vascular tone and membrane potential in vascular smooth muscle cells (Blaustein, 1993 and Marín and Redondo, 1999). We previously reported that a 7-day treatment with a low concentration of lead acetate increased the protein expression of the Na+/K+-ATPase alpha-1 subunit and Na+/K+-ATPase activity in the rat aorta (Fiorim et al., 2011). K+-induced relaxation was used as an index of Na+/K+-ATPase functional activity (Weeb and Bohr, 1978). Endothelium removal and the non specific NOS inhibitor L-NAME reduced such relaxation more in aortic rings from

lead-treated compared to the untreated rats, and the iNOS inhibitor aminoguanidine only had effect in rings from treated rats. These findings suggest that the increased of Na+/K+-ATPase

functional activity induced by lead could be mediated by the NO pathway. In addition to guanylate cyclase activation, NO is also a hyperpolarizing factor that increases K+ channel permeability (Bolotina et al., 1994 and Félétou and Vanhoutte, 2006). Our results showed that the non specific K+ channels blocker TEA did not modify K+-induced relaxation in the aortas from untreated rats but reduced it in treated rats. After co-incubation of the rings with TEA plus OUA, K+-induced relaxation was not different between the groups, suggesting a similar action between K+ channels and Na+/K+ATPase activity in the lead-treated rats. Lead treatment did not modify ACh-induced relaxation in phenylephrine pre-contracted aortas, 5-Fluoracil supplier as previously reported (Fiorim et al., 2011). The importance of endothelial NO in controlling vascular tone in conductance arteries is well established (Urakami-Harasawa et al., 1997 and Félétou and Vanhoutte, 2006). In agreement, we found that ACh-induced relaxation in the aorta was entirely dependent on NO release because it was abolished by L-NAME. As mentioned, NO can also hyperpolarize vascular smooth muscle cells by activating different K+ channels, depending on the vascular bed or species studied (Bolotina et al., 1994, Félétou and Vanhoutte, 2006, Félétou and Vanhoutte, 2009 and Félétou et al., 2010).