In vitro effects of arginine or citrulline associated with a statine on nitrite oxide (NO) production in bovine aortic endothelial cells (BAECs)

Introduction Endothelial dysfunction occured very early in atherogenesis. It is due to decrease in NO production by endothelial cells leading to loss of vasodilation. NO is synthetised in endothelial cells by the endothelial nitric oxide synthase (eNOS) from arginine, with production of citrulline. Citrulline can be recycled in arginine, via arginino succinate synthase (ASS) and arginino succinate lyase (ASL). Moreover, statine increases eNOS activity and synthesis and therefore improves endothelial function. Materials and methods NO was determined using a nitrate and nitrite fluorimetric assay. Results NO production was increased in the presence of simvastatine and arginine or citrulline. This increase was more important with arginine compared to citrulline at 1mM. Without any substrate in the medium, an increase in eNOS protein level was found. In the presence of arginine 1mM, the simvastatine effect on eNOS protein level was more pronounced than in the presence of arginine 0,5mM. The effect was found also in the presence of citrulline 1mM. The same results were observed with eNOS mRNA level. Finally, when cells were incubated with arginine 0,5mM, simvastatine lead to increase ASL and ASS mRNA expression. Conclusion The association of substrate with simvastatine induces an increase NO production, compared with arginine or citrulline or statine only, which is in agreement with the increase in BAECs of eNOS mRNA and protein levels.