URINARY ACTIVE KALLIKREIN EXCRETION AND DIABETIC RENAL IMPAIRMENTS INSTREPTOZOTOCIN-TREATED RATS

To assess possible roles of the renal kallikrein-kinin system in the d evelopment of renal impairments in diabetes mellitus, we determined da ily excretion of urinary total and active kallikrein in uninephrectomi zed Wistar-Kyoto rats made diabetic by streptozotocin (45 mg/kg) as a bolus injection. We also evaluated the effect of captopril (50 mg/kg/d ay) administered orally on the development of diabetic renal impairmen ts in the streptozotocin-treated rats. Active kallikrein was determine d by its kininogenase activity, and generated kinins were radioimmunol ogically measured. Total kallikrein was also determined by measuring k ininogenase activity after inactive kallikrein had been activated with trypsin (200 mug/ml). Urinary active kallikrein excretion was signifi cantly reduced in streptozotocin-treated rats whereas urinary total ka llikrein excretion was unchanged, resulting in the decreased ratio of active to total kallikrein compared to that in the controls. These red uctions were preceded by the increased excretion of urine protein meas ured 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 ac tive kallikrein excretion, and the ratio of active to total kallikrein . Thus the results of this study indicate that the renal kallikrein-ki nin system might not play major roles in the development of diabetic r enal 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, t hey suggest that the renoprotective effects of captopril may be indepe ndent of the activation of renal kallikrein system in streptozotocin-t reated rats.