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Renal mechanisms of antihypertensive effects caused by inhibition of soluble epoxide hydrolase in Cyp1a1‐Ren‐2 transgenic rats.
Author(s) -
Kopkan Libor,
Honetschlagerová Zuzana,
Husková Zuzana,
Imig John D,
Hwang Sung H,
Hammock Bruce D,
Cervenka Ludek
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1016.4
Subject(s) - epoxide hydrolase 2 , chemistry , endocrinology , medicine , blood pressure , proteinuria , kidney , epoxide hydrolase , excretion , enzyme , biochemistry , microsome
We examined the hypothesis that antihypertensive responses to inhibition of soluble epoxide hydrolase (sEH) are mediated by natriuretic effects of increased epoxyeicosanoids in transgenic rats with inducible expression of the mouse renin gene [strain name Cyp1a1‐Ren‐2]. Hypertension was induced in Cyp1a1‐Ren‐2 rats through dietary administration of indole‐3‐carbinol (I3C; 0.3%) for 11 days. The sEH inhibitor, cis ‐4‐[4‐(3‐Adamantan‐1‐yl‐ureido)‐cyclohexyloxy]‐benzoic acid ( c ‐AUCB, 13 mg/L) was given in drinking water. Blood pressure (BP) was monitored by radiotelemetry in conscious animals (n=6‐8). Sodium excretion and proteinuria were determined in 24 hour urine samples. c ‐AUCB had no effects in non‐induced normotensive group. However, at the end of experimental period, c‐AUCB treatment attenuated the development of hypertension induced by I3C (systolic BP 181 ± 4 vs. 202 ± 5 mmHg, p<0.05), the loss in body weight (254 ± 4 vs. 228 ± 3 g, p<0.05) and proteinuria (27 ± 2 vs. 34 ± 3 mg/day, p<0.05) when compared with untreated rats. Moreover, c ‐AUCB induced natriuretic responses in treated rats (0.79 ± 0.06 vs. 0.57 ± 0.07 mmol/day, p<0.05) compared to untreated group. These data suggest that antihypertensive responses to inhibition of soluble epoxide hydrolase in these transgenic rats are mediated by the natriuretic and renoprotective effects in the kidney.