In the present study, we examined the effects of soluble epoxide hydrolase (sEH) inhibition on the development of angiotensin II-dependent hypertension and on renal function in transgenic rats with inducible expression of the mouse renin gene (strain name Cyp1a1-Ren-2). Hypertension was induced in these rats by indole-3-carbinol (I3C; 0.3% in the diet) for 12 days. The sEH inhibitor cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) was given in two doses (13 or 26 mg l-1) in drinking water. Blood pressure (BP), body weight (BW) and renal excretory parameters were monitored in conscious animals during the experiment. Renal haemodynamics was assessed at the end of treatment in anaesthetized rats. I3C administration resulted in severe hypertension with a rise in systolic BP from 118 ± 2 to 202 ± 3 mmHg, a loss of BW from 266 ± 5 to 228 ± 4 g and a rise in proteinuria from 14 ± 2 to 34 ± 3 mg day-1. Both doses of c-AUCB significantly attenuated the development of hypertension (systolic BP of 181 ± 4 and 176 ± 4 mmHg, respectively), the loss in BW (256 ± 4 and 259 ± 3 g, respectively) and the degree of proteinuria (27 ± 2 and 25 ± 3 mg day-1, respectively) to a similar extent. Moreover, c-AUCB prevented the reduction in renal plasma flow (5.4 ± 0.4 vs. 4.6 ± 0.3 ml min-1 g-1) and significantly increased sodium excretion (0.84 ± 0.16 vs. 0.38 ± 0.08 μmol min-1 g-1) during I3C administration. These data suggest that the oral administration of c-AUCB displays antihypertensive effects in Ren-2 transgenic rats with inducible malignant hypertension via an improvement of renal function.

• MeSH
• Angiotensin II MeSH
• Antihypertensive Agents administration & dosage   pharmacology   MeSH
• Administration, Oral MeSH
• Benzoates administration & dosage   pharmacology   MeSH
• Time Factors MeSH
• Cytochrome P-450 CYP1A1 genetics   MeSH
• Epoxide Hydrolases antagonists & inhibitors   metabolism   MeSH
• Glomerular Filtration Rate drug effects   MeSH
• Hypertension chemically induced   enzymology   genetics   physiopathology   prevention & control   MeSH
• Enzyme Inhibitors administration & dosage   pharmacology   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Arachidonic Acids metabolism   MeSH
• Hydroxyeicosatetraenoic Acids metabolism   MeSH
• Kidney blood supply   drug effects   enzymology   physiopathology   MeSH
• Urea administration & dosage   analogs & derivatives   pharmacology   MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Promoter Regions, Genetic MeSH
• Proteinuria metabolism   physiopathology   prevention & control   MeSH
• Renal Plasma Flow drug effects   MeSH
• Renin genetics   metabolism   MeSH
• Sodium urine   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• 4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid MeSH Browser
• Angiotensin II MeSH
• Antihypertensive Agents MeSH
• Benzoates MeSH
• Cytochrome P-450 CYP1A1 MeSH
• EPHX2 protein, rat MeSH Browser
• Epoxide Hydrolases MeSH
• Enzyme Inhibitors MeSH
• Arachidonic Acids MeSH
• Hydroxyeicosatetraenoic Acids MeSH
• Urea MeSH
• Ren2 protein, mouse MeSH Browser
• Renin MeSH
• Sodium MeSH