To assess possible roles of the renal kallikrein-kinin system in the development of renal impairments in diabetes mellitus, we determined daily excretion of urinary total and active kallikrein in uninephrectomized Wistar-Kyoto rats made diabetic by streptozotocin (45 mg/kg) as a bolus injection. We also evaluated the effect of captopril (50 mg/kg/day) administered orally on the development of diabetic renal impairments in the streptozotocin-treated rats. Active kallikrein was determined by its kininogenase activity, and generated kinins were radioimmunologically measured. Total kallikrein was also determined by measuring kininogenase activity after inactive kallikrein had been activated with trypsin (200 μg/ml). Urinary active kallikrein excretion was significantly reduced in streptozotocin-treated rats whereas urinary total kallikrein excretion was unchanged, resulting in the decreased ratio of active to total kallikrein compared to that in the controls. These reductions were preceded by the increased excretion of urine protein measured as an index of renal impairments. The administration of captopril for 12 weeks attenuated the development of diabetic renal impairments evaluated by urine protein excretion in streptozotocin-treated rats, although it did not induce significant changes in urinary total and active kallikrein excretion, and the ratio of active to total kallikrein. Thus the results of this study indicate that the renal kallikrein-kinin system might not play major roles in the development of diabetic renal impairments in the rat, although the pathophysiological relevance of impaired activation of renal kallikrein system to the development of diabetic renal impairments remains to be determined. In addition, they suggest that the renoprotective effects of captopril may be independent of the activation of renal kallikrein system in streptozotocin-treated rats.
- active kallikrein excretion
- angiotensin converting enzyme inhibitors
- diabetic renal impairments
- experimental diabetes mellitus
- renal kallikrein-kinin system
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)