Early development of nephropathy in a new model of spontaneously hypertensive rat with non-insulin-dependent diabetes mellitus

M. Wakisaka, K. Nunoi, M. Iwase, M. Kikuchi, Y. Maki, K. Yamamoto, S. Sadoshima, M. Fujishima

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13 Citations (Scopus)


We designed the present study to clarify whether the development of nephropathy was accelerated by a combination of hypertension and non-insulin-dependent diabetes. Spontaneously hypertensive rats with non-insulin-dependent diabetes induced by neonatal streptozotocin treatment (25.0-75.0 mg/kg) were separated into severely or mildly diabetic groups according to their non-fasting plasma glucose levels at 12 weeks of age and the findings were compared with the data on a control group treated with citrate buffer alone. The natural courses of urinary excretion rate of total protein, the molecular composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis with laser desitometer and N-acetyl-β-D-glucosaminidase were measured in the three groups from 12 weeks until 36 weeks of age. Total urinary protein in the control group decreased with age (p<0.05), while in the mildly diabetic group changes were nil; in the severely diabetic group, however, the excretion rates of total urinary protein and high molecular weight protein consistently and progressively increased with age (p<0.05). The low molecular weight protein continuously decreased with age in the mildly diabetic and control groups (p<0.05), while in the severely diabetic group there was no decrease after 28 weeks of age. The urinary N-acetyl-β-D-glucosaminidase markedly increased (p<0.05) in the severely diabetic group throughout the period compared with findings in the control group, but drastically decreased (p<0.05) in the mildly diabetic group with age. There were significant correlations between the mean glycosylated haemoglobin levels and all the urinary parameters measured (p<0.05). These observations suggest that development of nephropathy is accelerated by the glycaemic level in hypertensive rats. This new model should be appropriate for studying the combined effects of hypertension and diabetes mellitus on the kidney.

Original languageEnglish
Pages (from-to)291-296
Number of pages6
Issue number5
Publication statusPublished - May 1988
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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