Renal Kallikrein and Hemodynamic Abnormalities of Diabetic Kidney

  1. Ronald K Mayfield
  1. Departments of Medicine and Pharmacology, Medical University of South Carolina, and the Veterans Administration Medical Center Charleston, South Carolina
  1. Address correspondence and reprint requests to Dr. Ronald K. Mayfield, Department of Medicine, 171 Ashley Avenue, Charleston, SC 29425.

Abstract

The relationship between renal hemodynamic abnormalities and renal kallikrein activity was studied in streptozocin-induced diabetic rats. Diabetic rats were either not treated with insulin and had plasma glucose levels >400 mg/dl (severely hyperglycemic diabetic [MD]) or were treated with 1.5–1.75 U/day protamine zinc insulin and had glucose levels of 200–300 mg/dl (moderately hyperglycemic diabetic [MD]). In SD rats, kidney tissue level and excretion of active kallikrein were reduced after 3 wk compared with age-matched nondiabetic control rats (tissue, 11.7 ± 1.9 vs. 20.5 ± 1.8 ng/mg protein, P <0.005; urine, 126 ± 12vs. 179 ± 10 μg/24 h, P <0.05). Glomerular filtration rate (GFR) was not significantly lower (2.77 ± 0.60vs. 3.02 ± 0.56 ml/min). In MD rats, kidney tissue level and excretion of active kallikrein were increased after 5 wk compared with age-matched nondiabetic control rats (tissue, 28.4 ± 1.3 vs. 23.3 ± 1.7 ng/mg protein, P < 0.05; urine, 289 ± 16 vs. 196 ± 13μg/24 h, P < 0.001). In MD rats, GFR and RPF were increased (3.80 ± 0.11 and 8.04 ± 0.17 ml/min, respectively) compared with control rats (3.22 ± 0.05 and 7.28 ± 0.09 ml/min, P < 0.001). Treatment of MD rats with a kallikrein inhibitor reduced GFR and RPF to levels similar to those of nondiabetic control rats. With recent evidence that kallikrein and kinins have a renal paracrine role in regulating vascular resistance, our findings suggest that altered kallikrein activity may contribute to the renal hemodynamic and filtration abnormalities in diabetes.

  • Received April 6, 1989.
  • Revision received October 30, 1989.
  • Accepted October 30, 1989.
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