To move or not to move? Cytochrome P450 products and cell migration.

Abstract

Over the last 5 to 8 years, researchers have begun to appreciate the prominent role played by cytochrome P450 (CYP) enzymes in the regulation of vascular tone, homeostasis, and blood pressure. For example, interfering with CYP genes markedly affects blood pressure in mice,1 and numerous reports have demonstrated that CYP expression is altered in genetic and experimental models of hypertension (for a recent review, see Moreno et al2). Vascular CYP enzymes can be divided into two classes, the epoxygenases, which metabolize arachidonic acid to a series of regiospecific and stereospecific epoxides (5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids or EETs), which are potent vasodilators, and the ω-hydroxylases, which generate the vasoconstrictor eicosanoid, 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is thought to mediate the myogenic response as well as the contraction induced by a number of contractile agonists and is generally assumed to augment basal blood pressure.3 EETs, on the other hand, are potent vasodilators and play a central role in the nitric oxide– and prostacyclin-independent relaxation of coronary, renal, and cerebral arteries. Although identified as potential endothelium-derived hyperpolarizing factors (EDHFs), it is now appreciated that EETs regulate much more than vascular tone and are in fact intracellular signal transduction molecules that have a central function in the regulation of vascular homeostasis.4 The effects of EETs can be attributed to their ability to activate a number of signal transduction pathways (in addition to those responsible for the activation of Ca2+-dependent K+ channels and hyperpolarization) in endothelial as well as vascular smooth muscle cells (Figure). A number …