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The placenta vascular bed represents a low pressure, high flow circulation whose main regulatory point are the chorionic arteries. Due to the lack of placenta innervation, hormonal and local factors, such as those derived from the endothelium (i.e. nitric oxide (NO) released by the endothelial NO Synthase (eNOS)), exert an effective control on local vascular tone. The eNOS activity is highly dependent on the availability of L-arginine. Thus, enzymes related with the metabolism of this amino acid, such as arginases, have recently risen as determinant factors that could regulate endothelial NO synthesis leading to modulation of vascular function. Arginase II is the major isoform expressed in human endothelial cells in several vascular beds including the placenta. Its expression is up-regulated by hypoxia, a clinical condition associated with pregnancy diseases including intrauterine growth restriction (IUGR) and pre-eclampsia. During the last years it has been shown that the expression of proteins crucial for endothelial function is controlled by a distinctive pattern of epigenetic modifications present in histones and DNA. Moreover, endothelial cell phenotypes are highly influenced by environmental stimuli, at determined points of development, such as oxygen levels or blood flow, both of them altered in IUGR. According to these ideas we thereby propose that the increased vascular tone in IUGR placentae is due to a decreased NO-induced vasodilatation in chorionic arteries that result from high levels and activity of arginase II paralleled to low levels and activity of eNOS. Changes in the expression patterns of arginase II and eNOS are controlled by epigenetic modifications in DNA and histones.