Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren-2 transgenic hypertensive rats
PBN-AR
Instytucja
Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
ISSN
0305-1870
EISSN
1440-1681
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2014
Numer zeszytu
3
Strony od-do
227-237
Numer tomu
41
Identyfikator DOI
Liczba arkuszy
1,88
Słowa kluczowe
en
5 6 nephrectomy chronic kidney disease cytochrome P450 enzymes end-organ damage epoxyeicosatrienoic acids hypertension renin-angiotensin system soluble epoxide hydrolase
Streszczenia
Język
en
Treść
<list list-type=''1'' id=''cep12204-list-0001''> The aim of the present study was to test the hypothesis that increasing kidney tissue concentrations of epoxyeicosatrienoic acids (EETs) by preventing their degradation to the biologically inactive dihydroxyeicosatrienoic acids (DHETEs) using blockade of soluble epoxide hydrolase (sEH) would attenuate the progression of chronic kidney disease (CKD). Ren-2 transgenic rats (TGR) after 5/6 renal mass reduction (5/6 NX) served as a model of CKD associated with angiotensin (Ang) II-dependent hypertension. Soluble epoxide hydrolase was inhibited using cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB; 3mg/L drinking water) for 20weeks after 5/6 NX. Sham-operated normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. When applied in TGR subjected to 5/6 NX, c-AUCB treatment improved survival rate, prevented the increase in blood pressure, retarded the progression of cardiac hypertrophy, reduced proteinuria and the degree of glomerular and tubulointerstitial injury and reduced glomerular volume. All these organ-protective actions were associated with normalization of the intrarenal EETs:DHETEs ratio, an index of the availability of biologically active EETs, to levels observed in sham-operated HanSD rats. There were no significant concurrent changes of increased intrarenal AngII content. Together, these results show that 5/6 NX TGR exhibit a profound deficiency of intrarenal availability of active epoxygenase metabolites (EETs), which probably contributes to the progression of CKD in this model of AngII-dependent hypertension, and that restoration of intrarenal availability of EETs using long-term c-AUCB treatment exhibits substantial renoprotective actions.
Cechy publikacji
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Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Original article
Original article presents the results of original research or experiment.
Inne
System-identifier
PBN-R:590341
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