Renal mechanisms contributing to the antihypertensive action of soluble epoxide hydrolase inhibition in Ren-2 transgenic rats with inducible hypertension. J Physiol 2011 Jan 01;589(Pt 1):207-19
Date
11/17/2010Pubmed ID
21078594Pubmed Central ID
PMC3039270DOI
10.1113/jphysiol.2010.199505Scopus ID
2-s2.0-78650367090 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Honetschlägerová Z, Husková Z, Vaňourková Z, Sporková A, Kramer HJ, Hwang SH, Tsai HJ, Hammock BD, Imig JD, Červenka L, Kopkan LMESH terms used to index this publication - Major topics in bold
Administration, OralAngiotensin II
Animals
Antihypertensive Agents
Arachidonic Acids
Benzoates
Blood Pressure
Cytochrome P-450 CYP1A1
Disease Models, Animal
Enzyme Inhibitors
Epoxide Hydrolases
Glomerular Filtration Rate
Hydroxyeicosatetraenoic Acids
Hypertension
Kidney
Male
Mice
Promoter Regions, Genetic
Proteinuria
Rats
Renal Plasma Flow
Renin
Sodium
Time Factors
Urea
