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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.
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PMID:A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy. 135 Sep 91

Glomerular ultrafiltration coefficient, Kf, is diminished in established diabetic nephropathy. To determine whether Kf is decreased because of a decrease in capillary area, A, and or in hydraulic conductivity, Lp, glomerular Kf and morphometric parameters were measured, and Lp was calculated in glomeruli of young rats with STZ-induced DM and in control rats. STZ was administered to Fischer 344 rats that weighted 50-75 g; glomeruli were examined after 3 or 5 mo of DM, and their structure and function was compared with that of control rats. The effects of insulin or of an ACEI, enalapril, also were assessed after 3 or 5 mo. Growth of DM rats was markedly impaired, and their ratio of kidney weight to body weight was increased. Ccr was proportional to rat weight, and the ratio of Ccr to body weight was not different in DM and control rats. At 3 mo, average volume of glomeruli isolated from DM rats was less than that of glomeruli from control rats. In contrast, glomerular volume after 5 mo was equal in DM and control rats. No increase in GBM thickness or mesangial volume was observed, nor was any decrease seen in GBM area in DM rats at 5 mo. Kf was lower in DM rats than controls after 3 mo, but not after 5 mo. The Lp of DM and control glomeruli did not differ at 3 mo, but was lower in DM at 5 mo. Insulin therapy improved somatic growth and increased kidney and glomerular size in DM rats; the kidney weight/body weight ratio remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diminished glomerular capillary hydraulic conductivity precedes morphologic changes in experimental diabetes mellitus in the rat. 149 63

Several lines of evidence suggest that hypertension is a contributing factor to diabetic nephropathy, a major cause of mortality in diabetes mellitus patients. The present study tested the hypotheses (1) that insulin dependent diabetes (IDD) causes hypertension, and (2) that simultaneous hypertension and IDD causes greater renal damage than would be expected from the independent contributions of each disease. IDD was induced by injection of streptozotocin (STZ, 65 mg/kg i.p.) into male Wistar rats, causing severe hyperglycaemia within 4 days. Seven days after the STZ treatment, hypertension was initiated by subcutaneous implantation of deoxycorticosterone acetate and administration of 1% saline in the drinking water (DOCA-NaCl). IDD rats not receiving DOCA-NaCl displayed a small elevation of blood pressure one week after STZ treatment, but thereafter displayed significant hypotension. The IDD rats receiving DOCA-NaCl displayed elevated systolic arterial pressure throughout the study, but by the end of the experiment, their mean systolic arterial pressure was significantly lower than that of the rats treated with DOCA-NaCl alone. Only the IDD/DOCA-NaCl rats displayed significant signs of renal dysfunction, i.e. greatly increased proteinuria and morphological renal damage, including marked distension of distal tubules and occasional casts. No other group displayed these abnormalities.
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PMID:Effects of simultaneous diabetes and hypertension in an insulin dependent diabetic model. 176 11

Vanadate has been previously shown to normalize blood glucose in streptozotocin-induced diabetic (STZ-DM) rats. The effect of a previously studied dose of vanadate (0.8 mg/ml) in drinking water on blood glucose, renal hypertrophy, and whole kidney polyol accumulation was studied in STZ-DM rats. Rats with diabetes of 5 weeks duration had higher blood glucose, greater urinary output, higher kidney weight, lower body weight, and higher kidney to body weight ratios than controls. Whole kidney sorbitol concentrations were significantly increased in diabetes but myo-inositol levels were unchanged vs control animals. After four weeks of oral vanadate treatment, blood glucose, urine volume, and kidney weights were similar to control values. Kidney to body weight ratios fell below that of the STZ-DM animals, but because body weights remained decreased, the kidney to body weight ratios were not normalized. Renal sorbitol levels returned to control values and renal myo-inositol levels remained unchanged in STZ-DM and normal animals treated with vanadate. These results provide evidence that vanadate therapy may result in regression of the hypertrophy and polyol accumulation characteristic of diabetic nephropathy in STZ-DM rats. This effect is most likely due to normalization of blood glucose by the insulin-mimetic activity of vanadate treatment.
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PMID:Effect of vanadate on renal hypertrophy and sorbitol accumulation in streptozotocin induced diabetes in rats. 187 50

The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as well as for the initiation and progression of diabetic nephropathy are not fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been invoked in the former and thromboxane (TXB2) and hyperlipidemia in the latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid synthesis and serum lipid profiles. We therefore examined the effects of a FO-enriched diet on glomerular filtration (GFR), proteinuria, glomerular eicosanoid production, and serum lipids in rats with streptozotocin-induced DM (STZ-DM). Groups of 5-8 rats with STZ-DM were maintained on low insulin and then pair-fed with isocaloric diets enriched with either FO (20% w/w) or beef tallow (BT; 20% w/w). GFR was determined in the same animals at onset of diet and after 8 and 20 weeks on the respective diets by [14C]inulin clearance using implanted osmotic minipumps each time. Significant hyperfiltration was present initially and GFR did not change on either diet for 20 weeks, in spite of a significant and greater than 50% decrease in all prostaglandins (PGE2, TXB2, PGF2 alpha, 6-keto, PGF1 alpha) produced by glomeruli isolated from DM/FO as compared to DM/BT or control rats. FO diet completely corrected the hypertriglyceridemia of diabetes and significantly reduced the mild and early proteinuria of DM. The decrease in proteinuria and the correction of hyperlipidemia of DM by a FO-enriched diet may be beneficial in the long term not only for the development of diabetic glomerulopathy, but also for the accelerated atherosclerosis of DM.
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PMID:Effects of fish oil on glomerular function in rats with diabetes mellitus. 240 55

We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment with statil (an aldose reductase inhibitor). In another set of rats maintained for 7 mo, albuminuria was significantly increased in the diabetic rats from 2 mo on but was also not affected by statil treatment. Similarly, histological glomerular damage and diabetes-induced kidney hypertrophy were also greater in diabetic animals but were not altered by statil treatment. The frequency of diabetic cataracts was reduced by statil, and erythrocyte and kidney sorbitol levels were normalized, confirming the efficacy of ARI. Thus, inhibition of the aldose reductase pathway with statil does not ameliorate the hemodynamic, proteinuric, histological, or growth abnormalities in this model of diabetic nephropathy.
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PMID:Aldose reductase inhibition and glomerular abnormalities in diabetic rats. 250 60

Increased accumulation of renal sorbitol has been documented in the diabetic rat, and it has been suggested that this accumulation may be important in the pathogenesis of diabetic nephropathy. It is not clear whether sorbitol accumulation results from increases in substrate, activity of the aldose reductase (AR) protein molecule, or activity due to an increase in the amount of enzyme present. In this study, we have quantitated renal AR activity, immunoreactivity, and mRNA in rats 3 mo after induction of diabetes with streptozocin (STZ-D, 65 mg/kg body wt). Renal AR activity was significantly increased in diabetic rats compared with age-matched nondiabetic controls (0.95 +/- 0.05 vs. 0.51 +/- 0.03 U.mg-1.h-1, respectively, P less than .0005). Western blot analysis demonstrated that the antiserums recognized a single 40,000-Mr protein species in renal homogenates from both diabetic and nondiabetic rats. When quantitated in an immunodot assay, AR immunoreactivity was significantly increased in diabetic rats compared with nondiabetic controls (0.57 +/- 0.03 vs. 0.33 +/- 0.02 U, respectively, P less than .0005). Hybridization of Northern blots with a synthetic 36-nucleotide oligomer and an AR cDNA identified a 1.4-kilobase pair transcript; the abundance of the transcript was significantly increased in poly(A)+ RNA from the kidneys of diabetic compared with nondiabetic rats (P less than .005). This study demonstrates that renal AR activity is increased in the STZ-D rats and suggests that the increased AR activity can be in part explained by enhanced AR gene expression.
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PMID:Increased renal aldose reductase activity, immunoreactivity, and mRNA in streptozocin-induced diabetic rats. 252 63

To evaluate whether hypertension is a cause or just an association with diabetic renal disease, diabetes was induced in both normotensive Wistar-Kyoto and spontaneously hypertensive rats (WKY and SHR). Animals were assessed monthly for 8 months before sacrifice. When compared to normotensive diabetic rats (WKY-STZ), hypertensive diabetic rats (SHR-STZ) had an earlier and more rapid rise in urinary albumin excretion. In addition, SHR-STZ had increased glomerular basement membrane thickness when compared to WKY-STZ or SHR. In a separate experiment, Enalapril therapy (35 mg/L) was administered in drinking water to WKY-STZ and SHR-STZ. Enalapril significantly reduced blood pressure in both animal groups, and this was associated with a decrease in urinary albumin excretion. The SHR-STZ model has accelerated nephropathy as determined by both functional and structural parameters. Angiotensin-converting enzyme inhibition is associated with a reduction in albuminuria in both hypertensive and normotensive models of diabetic nephropathy.
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PMID:Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat. 283 66

Male Sprague-Dawley rats were fasted 18 h and given streptozocin (STZ; 60 mg/kg body wt i.p.). The resultant diabetes mellitus, not treated with insulin, was associated with persistent manifoldly increased plasma IgA levels, as measured by single-radial immunodiffusion after reduction with dithiothreitol and alkylation with iodoacetamide. Also observed were concurrent increases in plasma levels of secretory IgA (sIgA) and of C3- and IgA-containing immune complexes (C3-IgA-CIC). After 104 days without insulin treatment, six of the diabetic rats were given daily injections of 2 U of insulin for 11 days. Insulin treatment was associated with a precipitous decrease in plasma levels of IgA, sIgA, and C3-IgA-CIC. Cessation of insulin treatment resulted in restoration of greatly increased levels of all three IgA-containing species. Histoimmunofluorescence studies of kidneys from untreated rats with diabetes of 192-324 days revealed glomerular capillary wall and mesangial deposits reacting strongly with anti-IgA (alpha-chain-specific) antiserum. Kidneys from two of the diabetic rats (324 days) were tested with anti-rat C3 and anti-rat secretory component (SC) antisera, and they reacted positively. Control kidneys from normal rats examined simultaneously were negative. The concurrent changes in plasma levels of three IgA-containing species in the untreated STZ-induced diabetic rat and the demonstration of abnormal immunoreactive IgA-containing renal glomerular deposits make this experiment an attractive model for studying the possible role of disturbed IgA metabolism in the pathogenesis of diabetic nephropathy.
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PMID:Increased plasma IgA, sIgA, and C3- and IgA-containing immune complexes with renal glomerular deposits in diabetic rats. 296 34

Recent clinical reports have suggested that hypertension accelerates the progress of diabetic nephropathy and retinopathy, whereas antihypertensive treatments may retard them. Thus, the effect of antihypertensive treatment in diabetes mellitus with hypertension was evaluated in rats. A model of diabetes mellitus with hypertension has been developed in spontaneously hypertensive (SHR) rats by unilateral nephrectomy and streptozotocin (STZ, 30 mg/kg, i.v. treatment). The rats were treated with four antihypertensive drugs orally for 12 weeks thereafter. STZ treatment induced chronic hypeglycaemia (300-400 mg/dl), decreased body weight and heart rate, and caused vascular changes of ophthalmic fundi and cataracta. The kidney of these rats showed proliferative changes such as periarteritis nodosa, hyperplasia, or fibronecrosis of the arterioles, exudative changes, mesangial proliferation, or thickening of the basement membrane of the glomeruli. Enalapril (10 mg/kg per day) and remipril (Hoe 498) (1 mg/kg per day), converting enzyme inhibitors, or arotinolol (20 mg/kg per day), a beta-adrenoceptor blocking drug, decreased blood pressure, prevented the development of renal and ocular lesions, and tended to increase creatinine clearance. Nisoldipine (3 mg/kg per day), a calcium-entry blocking drug, tended to decrease blood glucose, and prevented the decrease of body weight and development of ocular lesions. In conclusion, antihypertensive treatments were effective in preventing the progress of diabetic retinopathy and nephropathy, and renal insufficiency in this animal model.
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PMID:Antihypertensive treatment in spontaneously hypertensive rats with streptozotocin-induced diabetes mellitus. 329 54


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