title: Inhibition of soluble epoxide hydrolase improves the impaired pressure-natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats.
abstract: OBJECTIVE
  In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats.
  
  
  METHODS
  Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48 h before initiating administration of the diet containing I3C. Rats were prepared for renal functional studies to evaluate in-vivo renal autoregulatory efficiency when RAP was gradually decreased by an aortic clamp.
  
  
  RESULTS
  I3C administration resulted in the development of severe hypertension which was associated with markedly lower basal RBF and GFR and substantially impaired autoregulatory efficiency as well as a suppression of the pressure-natriuresis relationship when compared with noninduced rats. Treatment with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF and GFR and the slope of pressure-natriuresis relationship. Treatment with losartan completely prevented the impaired autoregulation and pressure-natriuresis relationship as well as the development of hypertension in I3C-induced rats.
  
  
  CONCLUSIONS
  Our present findings indicate that chronic treatment with the sEH inhibitor c-AUCB substantially attenuates the development of malignant hypertension in I3C-induced rats likely via improvement of the renal autoregulatory efficiency and the pressure-natriuresis relationship.
authors: Department for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors: Zuzana
authors: Z
authors: Honetschlägerová
authors: Alexandra
authors: A
authors: Sporková
authors: Libor
authors: L
authors: Kopkan
authors: Zuzana
authors: Z
authors: Husková
authors: Sung H
authors: SH
authors: Hwang
authors: Bruce D
authors: BD
authors: Hammock
authors: John D
authors: JD
authors: Imig
authors: Herbert J
authors: HJ
authors: Kramer
authors: Petr
authors: P
authors: Kujal
authors: Zdenka
authors: Z
authors: Vernerová
authors: Věra C
authors: VC
authors: Chábová
authors: Vladimír
authors: V
authors: Tesař
authors: Luděk
authors: L
authors: Cervenka
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006974:Hypertension, Malignant / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007211:Indoles / Q000009:adverse effects; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology / Q000517:prevention & control*; D019808:Losartan / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000235:genetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D007211:Indoles; C535029:Ren2 protein, rat; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; D004851:Epoxide Hydrolases; D012083:Renin; D019808:Losartan