Hyperlipidaemia and the Progression of Nephropathy in Oletf Rats: Effect of Angiotensin‐converting Enzyme Inhibitor, Enalapril

Sugimoto, Koh‐ichi; Tsuruoka, Shuichi; Fujimura, Akio

doi:10.1046/j.1440-1681.1999.03096.x

Cited by 10 publications

(10 citation statements)

References 27 publications

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“…Enalapril mildly, but significantly, lowered blood pressure in OLETF rats. In a previous study, enalapril did not affect renal haemodynamics, such as glomerular filtration rate or plasma renal flow, despite causing a significant fall in blood pressure 11 . Thus, it appears that enalapril may not affect whole kidney haemodynamics in OLETF rats under the present conditions.…”

Section: Discussioncontrasting

confidence: 42%

“…Enalapril, dissolved in distilled water, was given by gastric gavage once daily for 32 weeks. The dose of enalapril used in the present study was chosen on the basis of results of a previous study showing a significant renoprotective effect of this dose of enalapril in OLETF rats 11 . Enalapril maleate was purchased from Sigma Chemical Co. (St Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Enalapril, a non‐SH ACE inhibitor, has also been shown to have radical‐scavenging activity in diabetic patients 10 . We suggested previously that an improvement of the lipid profile is involved in the renoprotective effects of enalapril in Otsuka Long‐Evans Tokushima Fatty (OLETF) rats, a model of human type 2 diabetes mellitus associated with diabetic complications 11 . Increased oxidative stress increases oxidized low‐density lipoprotein, which may, in turn, promote glomerulosclerosis in diabetes 12 .…”

Section: Introductionmentioning

confidence: 99%

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Effect Of Enalapril On Diabetic Nephropathy In Oletf Rats: The Role Of An Anti‐Oxidative Action In Its Protective Properties

Sugimoto

Tsuruoka

Fujimura

2001

Clin Exp Pharma Physio

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1. We have evaluated the effects of the angiotensin-converting enzyme inhibitor enalapril on renal function and oxidative status in the kidney of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous onset of type 2 diabetes mellitus. 2. Enalapril (5 mg/kg) or vehicle (distilled water) was given once daily by gavage to 22-week-old male OLETF rats for 32 weeks. Long-Evans Tokushima Otsuka (LETO) rats, the control animals for OLETF rats, received vehicle alone (n = 10 in each group). 3. Enalapril attenuated the rise in blood pressure mildly, but significantly. Enalapril significantly blunted the development of proteinuria without a significant effect on creatinine clearance. At the end of the study period, the lipid peroxide content in the renal cortex was significantly increased in OLETF compared with LETO rats, in which enalapril had no effect on lipid peroxide content. Enalapril enhanced the activity of catalase in the renal cortex of OLETF rats, but had no effect on the activity of either superoxide dismutase or glutathione peroxidase. 4. These results suggest that oxidative stress may be involved in the development of nephropathy in type 2 diabetes. Enalapril exhibited renoprotective effects without changing lipid peroxides in the kidney, suggesting that the beneficial effects of the compound on diabetic renal damage in OLETF rats may not be mediated through an anti-oxidative action.

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Section: Discussioncontrasting

confidence: 42%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect Of Enalapril On Diabetic Nephropathy In Oletf Rats: The Role Of An Anti‐Oxidative Action In Its Protective Properties

Sugimoto

Tsuruoka

Fujimura

2001

Clin Exp Pharma Physio

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“…SHR/N-cp rats do not exhibit particularly severe hyperglycemia, but substantially elevated plasma cholesterol and particularly triglyceride concentrations. According to numerous experimental [41][42][43] and clinical observations, lipids, 44 particularly oxidised lipids, 45 cause glomerular injury. Finally, following the proposals of Brenner et al, 46,47 it is believed that a low number of glomeruli increases the risk of progression of renal disease.…”

Section: Comparison Of Stz and Shr/n-cp Model ML Gross Et Almentioning

confidence: 99%

Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

Groß

Ritz

Schoof

et al. 2004

Laboratory Investigation

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The Streptozotocin (STZ) model of diabetes is commonly used for studies of diabetic nephropathy although the histological lesions of the kidney are mild and do not resemble those seen in diabetic patients. The SHR/N-cp rat model of type II diabetes spontaneously develops pronounced abnormalities in renal histology. In the present study, we compared renal morphology in the STZ rat and the diabetic SHR/N-cp rat. Sprague-Dawley rats received STZ, developed diabetes after 2 days and were treated with insulin. In the SHR/N-cp rat, obesity is inherited as an autosomal recessive trait. The progeny are either lean (used as controls) or obese and diabetic. After 6 months of observation, STZ and SHR/N-cp rats were killed. The renal damage was evaluated by assessing damage indices and by using stereological techniques. In addition, immunohistochemistry and electron microscopy were performed. The glomerular and tubulointerstitial changes were much more pronounced in the diabetic SHR/N-cp compared to the STZ model. In parallel glomerular PCNA þ cells were significantly more frequent and expression of TGF-b and PDGF by immunohistochemistry in glomeruli and in the tubulointerstitial space was more pronounced in SHR/N-cp compared to STZ rats. The glomeruli of SHR/Ncp contained less and larger podocytes as well as smaller mesangial cells embedded in more mesangial matrix compared to STZ. Similarly, less, but larger endothelial cells were found in SHR/N-cp than in STZ rats. The mean glomerular volume was similarly increased in the two models. Albumin excretion was only modestly increased in STZ diabetes, but pronounced in the SHR/N-cp rat. Although the STZ model of diabetes exhibits numerous biochemical sequelae of hyperglycemia, the morphological lesions are unimpressive. In contrast, the diabetic SHR/N-cp exhibits marked structural lesions, particularly podocyte damage and mesangial expansion that promise to make it a more suitable model for investigation of diabetic glomerulosclerosis.

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“…The effect of the ACE inhibitor cilazapril on essential hypertension has been established. During the past 10 years there have been many reports showing the possibility that ACE inhibitors have a good effect on diabetic nephropathy [2,3] and cardiac complications [4]. The 'good effect' in clinical studies actually means that renal and cardiac functions remain stable or at least show no deterioration during treatment with the ACE inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Retinal and Choroidal Vasculature in Rats with Spontaneous Diabetes Type 2 Treated with the Angiotensin-Converting Enzyme Inhibitor Cilazapril: Corrosion Cast and Electron-Microscopic Study

Bhutto

Takami

et al. 2002

Ophthalmic Res

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The long-term effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on retinal and choroidal circulation in rats with spontaneous diabetes type 2 were assessed by corrosion casts, scanning electron microscopy (SEM) and transmission electron microscopy. One group of 20 male Otsuka Long-Evans Tokushima Fatty (OLETF) rats was treated with 10 mg/kg/day of cilazapril from 4 to 64 weeks of age, and 20 other OLETF rats received no treatment. A third group, 20 male Long-Evans Tokushima Otsuka (LETO) rats, served as age-matched controls. At regular intervals, the rats were weighed, and their blood glucose was measured. Before the experiment, their systolic blood pressure and total cholesterol level were determined. At 64 weeks of age, the OLETF rats weighed significantly less than the cilazapril-treated OLETF and the LETO rats (p < 0.0001). At the same age, 100% of the untreated OLETF rats had bilateral cataracts, while the lens was clear and no fundus abnormality was detected in the cilazapril-treated OLETF rats and the LETO rats. Cilazapril lowered systolic blood pressure to a nearly normal level, significantly prevented the increase in blood sugar and inhibited the increase in serum cholesterol in the OLETF rats throughout the treatment. In the 64-week-old OLETF rats without treatment, corrosion cast and SEM revealed diabetic retinal and choroidal vascular changes: tortuosity of the vessels, variations in caliber, narrowing of arteries, arterio-arteriolar anastomoses and hairpin loop formation in precapillary arterioles, sparse collecting venules in the choroid and marked capillary changes such as caliber irregularity, narrowing, tortuosity, loop formation and decreased capillaries, outpouching and microaneurysms. In the cilazapril-treated OLETF rats, these changes were markedly decreased to the level seen in the LETO rats, in which the retinal and choroidal blood vessels had a definite and fairly constant pattern and the capillaries were more regularly and densely arranged and had a remarkably uniform caliber. Our results show that the long-term administration of cilazapril before or from the initial onset significantly prevented the increase in blood sugar and inhibited the increases in serum cholesterol in OLETF rats throughout the treatment, lowered systolic arterial pressure to a nearly normal level and prevented diabetic ocular complications. The effects of cilazapril on the diabetic retinal and choroidal vasculature are described for the first time. SEM of corrosion casts is a valuable and easy technique for showing precisely and three-dimensionally the effects of some drugs on the vasculature.

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Hyperlipidaemia and the Progression of Nephropathy in Oletf Rats: Effect of Angiotensin‐converting Enzyme Inhibitor, Enalapril

Cited by 10 publications

References 27 publications

Effect Of Enalapril On Diabetic Nephropathy In Oletf Rats: The Role Of An Anti‐Oxidative Action In Its Protective Properties

Effect Of Enalapril On Diabetic Nephropathy In Oletf Rats: The Role Of An Anti‐Oxidative Action In Its Protective Properties

Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

Retinal and Choroidal Vasculature in Rats with Spontaneous Diabetes Type 2 Treated with the Angiotensin-Converting Enzyme Inhibitor Cilazapril: Corrosion Cast and Electron-Microscopic Study

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