Epoxyeicosatrienoic Acid Mimetics and Soluble Epoxide Hydrolase Inhibitors

EETs are vasodilatory metabolites and are described as EDHF Changes in the renal formation of EETs may also contribute to the development of AT-II hypertension with increased expression of soluble epoxide hydrolase (sEH), the enzyme responsible for EETs degradation in AT-II-infused rats.33 Expression of epoxygenase enzymes is increased in the kidney of rats fed a high-salt diet,36 while a deficiency in the renal formation of EETs may contribute to the development of AT-II-dependent forms of hypertension. Consistent with this, renal epoxygenase activity is reduced in transgenic rats overexpressing human renin and angiotensinogen genes.85 These animals develop severe hypertension and renal interstitial fibrosis and inflammation. Pharmacological blockade of sEH increases the urinary excretion of EETs and lowers blood pressure in both spontaneous hypertensive rats and AT-II hypertensive rats.86'87 Blood pressure is also reduced in sEH knockout mice in which production of EETs is elevated.88 Chronic administration of the orally active sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) (Figure 10), increased urinary EET excretion and reduced arterial pressure and renal damage in AT-II-mediated hypertension.89 Collectively, these studies suggest a potential role of EETs in lowering blood pressure and improving endothelial dysfunction.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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