20-hydroxyeicosatetraenoic acid, endothelial dysfunction and hypertension.

20-hydroxyeicosatrienoic acid (20-HETE) is a metabolite of arachidonic acid formed by the enzymatic activity of cytochrome P450 omega hydroxylases of the 4A and 4F isoform families (CYP 450 4A and 4F). The role of the metabolites of arachidonic acid (AA) formed by cyclooxygenases and lipoxygenases in mediating cardiovascular function have been studied and known for a long time. More recently, particularly in the last 10-15 years, the importance of the role that the CYP450 omega hydroxylase/20-HETE system plays in cardiovascular, inflammatory and neoplastic diseases, has captured the attention of the scientific community. In this brief review we discuss some of the more recent findings related to the function of 20-HETE in the cardiovascular system. In particular we focus on the interactions of 20-HETE with the intracellular pathways of nitric oxide and the renin angiotensin system and discuss how it plays a role in oxidative stress, the development of endothelial dysfunction and experimental and human hypertension. To date the research strongly suggests that 20-HETE is an important and central mediator of cardiovascular function, and that alterations in the normal regulation of the CYP450/20-HETE system play a role in the pathogenesis of many disorders. There is great potential for the development of therapeutic agents to modify the activation and activity of this system in order to prevent and/or treat hypertension.