The Potential of Soluble Epoxide Hydrolase Inhibition in the Treatment of Cardiac Hypertrophy

~:'~: mall molecule inhibitors of soluble .~). 'epoxide hydrolase (sEH) have been shown to reduce blood pressure, inflammation, and pain in a number of mammalian disease models. In fact, an inhibitor of sEH has been moved into clinical trials for the treatment of hypertension. The beneficial effect of sEH inhibition is thought to be due to the role of sEH in the metabolism of anti-inflammatory, antihypertensive, and analgesic lipid signaling molecules such as the epoxyeicosatrienoic acids. Recently, application of sEH inhibitors in animal models of cardiac hypertro­ phy have produced promising results. In this review, we describe these results and discuss the effect of sEH inhibitors on the inflammatory NF-lCB pathway and the implication this has for the treatment of cardiac hypertrophy. Inhibitors sEH are in clinical tri­ als as oral drugs for the treatment of hypertension. Based on animal mod­ els, sEHI appears to reduce the vascu­ lar inflammation and end-organ dam­ age that commonly are associated with hypertension. There appears to be a dramatic reduction in renal damage in angiotensin and deoxycorticosterone acetate-salt models of hypertension. Moreover, sEH inhibitors have been shown to have an anti-inflammatory action' and may be particularly useful in hypertensive patients, in whom it is important to control blood pressure in the presence of a systematic inflam­ matory disease. Animal models indi­ cate that sEH inhibitors, presumably working through epoxylipid chemical Todd R. Harris, PhD;! Ning Li, MS/ Nipavan Chiamvimonvat, MD/·3 Bruce D. Hammock, PhD' From the Department of Entomology and Cancer Center' and the Division of Cardiovascular Medicine, Department of Internal Medicine,2 University of California, Davis, CA; and the Department of Veterans Affairs, Northern California Health Care System, Mather, CN .