scholarly journals Effects of combined therapy of ACE inhibitor and exercise on the development of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats

2020 ◽  
Vol 9 (5) ◽  
pp. 235-246
Author(s):  
Shinichiro Aoyama ◽  
Daisuke Shindo ◽  
Junichi Otsuka ◽  
Eriko Matsuo ◽  
Shigeru Matsubara ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Ace Inhibitor ◽  
Combined Therapy ◽  
Long Evans

Unlike each drug alone, lisinopril if combined with avosentan promotes regression of renal lesions in experimental diabetes

2009 ◽  
Vol 297 (5) ◽  
pp. F1448-F1456 ◽  
Author(s):  
Elena Gagliardini ◽  
Daniela Corna ◽  
Carla Zoja ◽  
Fabio Sangalli ◽  
Fabiola Carrara ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Receptor Antagonist ◽  
Ace Inhibitor ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Diabetic Rats ◽  
Size Selectivity ◽  
Glomerular Lesions ◽  
Glomerular Size ◽  
And Function

In the present study, we evaluated the effect of simultaneously blocking angiotensin II synthesis and endothelin (ET)-1 activity as a multimodal intervention to implement renoprotection in overt diabetic nephropathy. Mechanisms underlying combined therapy effectiveness were addressed by investigating podocyte structure and function and glomerular barrier size-selective properties. Uninephrectomized rats made diabetic by streptozotocin received orally placebo, lisinopril (12.5 mg/l), the ETA receptor antagonist avosentan (30 mg/kg), or their combination from 4 (when animals had proteinuria) to 8 mo. Proteinuria, renal damage, podocyte number, nephrin expression, and glomerular size selectivity by graded-size Ficoll molecule fractional clearance were assessed. Combined therapy normalized proteinuria, provided complete protection from tubulointerstitial damage, and induced regression of glomerular lesions, while only a partial renoprotection was achieved by each drug alone. Lisinopril plus avosentan restored to normal values the number of podocytes. Single therapies only limited podocyte depletion. Defective nephrin expression of diabetes was prevented by each drug. Altered glomerular size selectivity to large macromolecules of diabetic rats was remarkably improved by lisinopril and the combined treatment. Avosentan ameliorated peritubular capillary architecture and reduced interstitial inflammation and fibrosis. The ACE inhibitor and ETA receptor antagonist induced regression of glomerular lesions in overt diabetic nephropathy. Regression of renal disease was conceivably the result of the synergistic effect of the ACE inhibitor of preserving glomerular permselective properties and the ETA antagonist in improving tubulointerstitial changes. These findings provide mechanistic insights to explain the antiproteinuric effect of this combined therapy in diabetes.

Combined Therapy of Rhein and Benazepril on the Treatment of Diabetic Nephropathy in db/db Mice

2007 ◽  
Vol 115 (09) ◽  
pp. 571-576 ◽  
Author(s):  
Z. Jia ◽  
Z. Liu ◽  
J. Zheng ◽  
C. Zeng ◽  
L. Li
Keyword(s):  
Diabetic Nephropathy ◽  
Combined Therapy

Effects of ACE-Inhibitor on Diabetic Nephropathy During Exercise Therapy in OLETF Rats

2004 ◽  
Vol 36 (Supplement) ◽  
pp. S251-S252
Author(s):  
Masato Suzuki ◽  
Noriko Hozumi ◽  
Masaki Kimura ◽  
Hideki Yamauchi ◽  
Toshiaki Shibasaki
Keyword(s):  
Diabetic Nephropathy ◽  
Exercise Therapy ◽  
Ace Inhibitor ◽  
Oletf Rats

Combined Therapy with Benazepril and Amlodipine in the Treatment of Hypertension Inadequately Controlled by an ACE Inhibitor Alone

1997 ◽  
Vol 30 (4) ◽  
pp. 497-503 ◽  
Author(s):  
Roberto Fogari ◽  
Luigi Corea ◽  
Ondina Cardoni ◽  
Franco Cosmi ◽  
Carlo Porcellati ◽  
...  
Keyword(s):  
Ace Inhibitor ◽  
Combined Therapy ◽  
Treatment Of Hypertension

scholarly journals Modulation of Incipient Glomerular Lesions in Experimental Diabetic Nephropathy by Hypotensive and Subhypotensive Dosages of an ACE Inhibitor

Diabetes ◽  
2001 ◽  
Vol 50 (11) ◽  
pp. 2619-2624 ◽  
Author(s):  
B. Fabris ◽  
R. Candido ◽  
M. Carraro ◽  
F. Fior ◽  
M. Artero ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Ace Inhibitor ◽  
Glomerular Lesions

Iron restriction prevents diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rat

Renal Failure ◽  
2013 ◽  
Vol 35 (8) ◽  
pp. 1156-1162 ◽  
Author(s):  
Mika Matsumoto ◽  
Naoko Sasaki ◽  
Takeshi Tsujino ◽  
Hirokuni Akahori ◽  
Yoshiro Naito ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Iron Restriction ◽  
Long Evans

Meprin-α in chronic diabetic nephropathy: interaction with the renin-angiotensin axis

2005 ◽  
Vol 289 (4) ◽  
pp. F911-F921 ◽  
Author(s):  
Roy Mathew ◽  
Stephen Futterweit ◽  
Elsa Valderrama ◽  
Antonio A. Tarectecan ◽  
John E. Bylander ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Protein Expression ◽  
Protein Content ◽  
Ace Inhibitor ◽  
Inhibitor Therapy ◽  
Treated Water ◽  
Renin Angiotensin ◽  
Gene And Protein Expression ◽  
The Impact

Meprin (MEP) A is a metalloendopeptidase that is present in the renal proximal tubule brush-border membrane (BBM) and that colocalizes with angiotensin-converting enzyme (ACE). The MEP β-chain gene locus on chromosome 18 has been linked to a heightened risk of diabetic nephropathy (DN) in patients with type 2 diabetes. This study evaluated 1) whether MEP-α and MEP-β gene and protein expression are altered in db/db mice before the onset of DN and 2) the role of MEP-α in the pathogenesis of DN and the impact of the renin-angiotensin system on this interaction in two experimental models of diabetes. MEP-α and MEP-β gene and protein expression were evaluated in db/db mice, 13–14 wk of age, compared with lean C57BLKS/J littermate animals. A treatment study was then performed in which db/db mice and controls were assigned to one of three groups: control (C) water, no therapy; ACE inhibitor therapy, enalapril (EN)-treated water, 50 mg/l; ANG II receptor type 1 blocker (ARB) therapy, losartan (LOS)-treated water, 500 mg/l. Treatment was started at 8 wk of age and continued for 52 wk. Male Sprague-Dawley rats with diabetes for 52 wk following a single dose of streptozocin (STZ; 60 mg/kg) were also studied. At 13.5 wk of age, MEP-α and MEP-β kidney mRNA abundance and protein expression were significantly lower in db/db mice compared with lean controls, with greater changes in MEP-β ( P < 0.05). In the treatment study, EN ameliorated and LOS exacerbated DN in db/db mice. BBM MEP A enzymatic activity and MEP-α protein content were lower in db/db mice vs. control nonobese mice at 52 wk ( P < 0.02). EN-treated db/db mice showed increased MEP A activity, MEP-α content in BBM, decreased urinary MEP-α excretion, and enhanced BBM staining for MEP-α protein vs. C and LOS-treated db/db mice. In nonobese mice, EN and LOS treatment had no effect on MEP-α expression. In rats with STZ-induced diabetes for 52 wk, urinary MEP-α excretion was increased and MEP A activity and MEP-α protein content per milligram of BBM protein were decreased compared with age-matched control animals ( P < 0.05). These results indicate that db/db mice manifest decreased MEP-α and MEP-β gene and protein expression, before the development of overt kidney disease. Moreover, in db/db mice with DN and rats with STZ-diabetes, there was an inverse relationship between renal MEP-α content and the severity of the renal injury. Treatment with an ACE inhibitor was more effective than ARB in ameliorating DN in db/db mice, a change that correlated with alterations in urinary excretion and BBM content of MEP-α. MEP-α may play a role in the pathogenesis of DN and the benefits of ACE inhibitor therapy on the progression of diabetic kidney disease may be related, in part, to its impact on renal MEP-α expression.

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