Soluble Epoxide Hydrolase Is a Main Effector of Angiotensin II–Induced Hypertension

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Abstract
The soluble epoxide hydrolase (sEH) metabolizes vasodilatory epoxyeicosatrienoic acids (EETs) to their di-hydroxy derivatives. We hypothesized that the metabolism of EETs by the sEH contributes to angiotensin II–induced hypertension and tested the effects of a water-soluble sEH inhibitor, 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) on blood pressure. AUDA (130 μg/mL in drinking water) did not affect blood pressure in normotensive animals but markedly lowered it in mice with angiotensin II–induced hypertension (1 mg/kg per day). The effect of AUDA was accompanied by an increase in urinary salt and water excretion. Intravenous application of AUDA (8 mg/kg) acutely lowered blood pressure and heart rate in animals with angiotensin II–induced hypertension but failed to affect blood pressure in animals with phenylephrine-induced hypertension (29 mg/kg per day). AUDA (0.1 μmol/L) selectively lowered vascular resistance in an isolated perfused kidney preparation from angiotensin II–pretreated mice but not...