Endothelial NOS is the main enzyme responsible for the production of NO, which counteracts the vasoconstricting effect of adrenergic hormone and neurological signals.45 Decreased cellular NO production may lead to endothelial cell apoptosis.46 Thus, the results from our in vitro experiments suggest that L5 may cause endothelial dysfunction by suppressing the phosphorylation of eNOS, which may in turn reduce NO production in patients and animals with uremia.47,48. This evidence concerns the gene NOS3 and uremia.