New rat model induced by anti‐glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end‐stage renal failure

Nakano, Yoshimasa; Hirano, Takahiro; Uehara, Kenji; Nishibayashi, Seiji; Hattori, Katsuji; Aihara, Miki; Yamada, Yoshihisa

doi:10.1111/j.1440-1827.2008.02237.x

Cited by 19 publications

(16 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sections were stained with haematoxylin–eosin and PAS and were examined and evaluated in a blinded manner. Fifty glomeruli in each kidney were examined on a semiquantitative scale as follows: Grade 0, all glomeruli normal; Grade 1, sclerotic area up to 25% (minimal sclerosis); Grade 2, sclerotic area 25–50% (moderate sclerosis); Grade 3, sclerotic area 50–75% (moderate‐to‐severe sclerosis); and Grade 4, sclerotic area 75–100% (severe sclerosis). The GSI was calculated as follows:

\begin{matrix} GSI & = [false(1 \times n_{1} false) + false(2 \times n_{2} false) + false(3 \times n_{3} false) + false(4 \times n_{4} false)] / \\ (n_{0} + n_{1} + n_{2} + n_{3} + n_{4}) \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren‐2 transgenic hypertensive rats

Kujal

Chábová

Škaroupková

et al. 2014

Clin Exp Pharma Physio

View full text Add to dashboard Cite

SUMMARY The aim of the present study was to test the hypothesis that increasing kidney tissue epoxyeicosatrienoic acids (EETs) concentration 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 II (ANG II)-dependent hypertension. sEH was inhibited using cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/l of drinking water) for 20 weeks after 5/6 NX. Sham-operated normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. c-AUCB treatment when applied in TGR subjected to 5/6 NX improved the rats’ 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 the glomerular volume, All these organ-protective actions were associated with normalization of the intrarenal EETs/DHETEs ratio, an index of availability of biologically active EETs, to levels observed in sham-operated HanSD rats. There were no significant concurrent alterations of increased intrarenal ANG II content. Taken together, these results show that, first, 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 ANG II-dependent hypertension. Second, restoration of intrarenal availability of EETs using long-term c-AUCB treatment exhibits substantial renoprotective actions.

show abstract

\begin{matrix} GSI & = [false(1 \times n_{1} false) + false(2 \times n_{2} false) + false(3 \times n_{3} false) + false(4 \times n_{4} false)] / \\ (n_{0} + n_{1} + n_{2} + n_{3} + n_{4}) \end{matrix}

…”

Section: Methodsmentioning

confidence: 99%

“…Renal cortical tubulointerstitial injury was evaluated as described by Nakano et al . and as used in our recent studies to determine inflammatory cell infiltration, tubular dilatation, atrophy or interstitial fibrosis.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren‐2 transgenic hypertensive rats

Kujal

Chábová

Škaroupková

et al. 2014

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Tubulointerstitial injury was evaluated as defined by Nakano et al [26] At least 30 random and nonoverlaping cortical fields were evaluated using 20 × objective. Tubulointerstitial injury was defined as tubular dilatation, atrophy, cast formation and sloughing of tubular epithelial cells or thickening of tubular basement membrane and scaring as follows grade 0, no injury; grade 1, tubulointerstitial injury in less than 25%; grade 2, (25–50%); grade 3, (>50%).…”

Section: Methodsmentioning

confidence: 99%

Antihypertensive and renoprotective actions of soluble epoxide hydrolase inhibition in ANG II-dependent malignant hypertension are abolished by pretreatment with L-NAME

Honetschlägerová

Kitada

Husková

et al. 2013

Journal of Hypertension

View full text Add to dashboard Cite

Objective The present study was performed to investigate in a model of malignant hypertension if the antihypertensive actions of soluble epoxide hydrolase (sEH) inhibition are nitric oxide (NO)-dependent. Methods ANG II-dependent malignant hypertension was induced through dietary administration for 3 days of the natural xenobiotic indole-3-carbinol (I3C) in Cyp1a1-Ren-2 transgenic rats. Blood pressure (BP) was monitored by radiotelemetry and treatment with the sEH inhibitor [cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyl-oxy]-benzoic acid (c-AUCB)] was started 48h before administration of the diet containing I3C. In separate groups of rats, combined administration of the sEH inhibitor and the nonspecific NO synthase inhibitor [Nω-nitro-l-arginine methyl ester (L-NAME)] on the course of BP in I3C-induced and noninduced rats were evaluated. In addition, combined blockade of renin–angiotensin system (RAS) was superimposed on L-NAME administration in separate groups of rats. After 3 days of experimental protocols, the rats were prepared for renal functional studies and renal concentrations of epoxyeicosatrienoic acids (EETs) and their inactive metabolites dihydroxyeicosatrienoic acids (DHETEs) were measured. Results Treatment with c-AUCB increased the renal EETs/DHETEs ratio, attenuated the increases in BP, and prevented the decreases in renal function and the development of renal damage in I3C-induced Cyp1a1-Ren-2 rats. The BP lowering and renoprotective actions of the treatment with the sEH inhibitor c-AUCB were completely abolished by concomitant administration of L-NAME and not fully rescued by double RAS blockade without altering the increased EETs/DHETEs ratio. Conclusion Our current findings indicate that the antihypertensive actions of sEH inhibition in this ANG II-dependent malignant form of hypertension are dependent on the interactions of endogenous bioavailability of EETs and NO.

show abstract

“…Cortical tubulointerstitial injury was evaluated as defined by Nakano et al [23] for inflammatory cell infiltration, tubular dilatation and/or atrophy, or interstitial fibrosis and was graded semi-quantitatively using the following scale: grade 0, no abnormal findings; 1, mild (<25 % of the cortex); 2, moderate (25 – 50 % of the cortex); 3, severe (>50 % of the cortex). Lesions were assessed for at least 30 random and non-overlapping fields in the renal cortex.…”

Section: Methodsmentioning

confidence: 99%

Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of epoxyeicosatrienoic acids degradation attenuates hypertension and hypertensioninduced end-organ damage in Ren-2 transgenic rats

Chábová

Walkowska

Kompanowska-Jezierska

et al. 2010

Clinical Science

View full text Add to dashboard Cite

Recent studies have shown that the renal cytochrome P-450 metabolites of arachidonic acid: the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE), and the vasodilator epoxyeicosatrienoic acids (EETs) play an important role in the pathophysiology of angiotensin II (ANG II)-dependent forms of hypertension and the associated target organ damage. The present studies were performed in Ren-2 renin transgenic rats (TGR) to evaluate the effects of chronic selective inhibition of 20-HETE formation or elevation of the level of EETs, alone or in combination, on the course of hypertension and hypertension-associated end-organ damage. Both young (30 days of age) prehypertensive TGR and adult (190 days of age) TGR with established hypertension were examined. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. The rats were treated with N-methylsulfonyl-12,12-dibromododec-11-enamide to inhibit 20-HETE formation and/or with N-cyclohexyl-N-dodecyl urea to inhibit soluble epoxide hydrolase and prevent degradation of EETs. Inhibition in TGR rats of 20-HETE formation combined with enhanced bioavailability of EETs attenuated the development of hypertension, cardiac hypertrophy, proteinuria, glomerular hypertrophy and sclerosis as well as renal tubulointerstitial injury. This was also associated with an attenuation of the responsiveness of the systemic and renal vascular beds to ANG II without modifying their responses to norepinephrine. Our data suggest that altered production and/or action of 20-HETE and EETs plays a permissive role in the development of hypertension and hypertension-associated end-organ damage in this model of ANG II-dependent hypertension. This information provides a basis for a search of new therapeutic approaches to the treatment of hypertension.

show abstract

New rat model induced by anti‐glomerular basement membrane antibody shows severe glomerular adhesion in early stage and quickly progresses to end‐stage renal failure

Cited by 19 publications

References 23 publications

Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren‐2 transgenic hypertensive rats

Inhibition of soluble epoxide hydrolase is renoprotective in 5/6 nephrectomized Ren‐2 transgenic hypertensive rats

Antihypertensive and renoprotective actions of soluble epoxide hydrolase inhibition in ANG II-dependent malignant hypertension are abolished by pretreatment with L-NAME

Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of epoxyeicosatrienoic acids degradation attenuates hypertension and hypertensioninduced end-organ damage in Ren-2 transgenic rats

Contact Info

Product

Resources

About