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Pharmaceuticals 2009, 2(3), 217-227; doi:10.3390/ph2030217

The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

1
Department of Pharmacology & Toxicology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2
Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
*
Author to whom correspondence should be addressed.
Received: 10 November 2009 / Revised: 12 December 2009 / Accepted: 16 December 2009 / Published: 18 December 2009
(This article belongs to the Special Issue Antihypertensive Drugs)
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Abstract

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.
Keywords: soluble epoxide hydrolase; eicosanoids; vascular; hypertension; kidney disease soluble epoxide hydrolase; eicosanoids; vascular; hypertension; kidney disease
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Imig, J.D.; Carpenter, M.A.; Shaw, S. The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension. Pharmaceuticals 2009, 2, 217-227.

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