Soluble
epoxide hydrolase inhibitors (sEHIs) are demonstrating promise as potential
pharmaceutical agents for the treatment of
cardiovascular disease, diabetes,
inflammation, and
kidney disease. The present study determined the ability of a first-inclass sEHI,
AR9281, to decrease blood pressure, improve vascular function, and decrease renal
inflammation and injury in
angiotensin hypertension. Rats were infused with
angiotensin and
AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and
AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in
angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in
angiotensin hypertension and two weeks of
AR9281 treatment decreased this index of renal
inflammation. Vascular function in
angiotensin hypertension was also improved by
AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by
AR9281 treatment of
angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI,
AR9281, lowers blood pressure, improves vascular function and reduces renal damage in
angiotensin hypertension.