Effects of heparin on vascular dysfunction in diabetic rats.

Abstract

1. Treatment with heparin has beneficial effects in diabetic nephropathy. The occurrence of increased urinary albumin excretion in diabetic patients reflects general vascular dysfunction, including increased transcapillary permeability of macromolecules. The aim of the present study was to evaluate the effects of heparin on vascular dysfunction in diabetic rats. 2. Male Sprague-Dawley rats were used in two studies. Diabetes was induced by 65 mg/kg, i.v., streptozotocin. In one study, diabetic rats were dosed subcutaneously with different heparin fractions for 8 months and the transcapillary escape rate of albumin (TERalb) was measured in anaesthetized animals. In the other study, heparin was given for 6 weeks, followed by tissue albumin clearance measurements in awake rats. Normal and diabetic rats receiving saline served as controls. 3. Blood glucose did not differ among the diabetic groups and ranged from 22 to 26 mmol/L. The mean (+/- SD) TERalb was increased by diabetes compared with values in normal rats (17.5 +/- 3 vs 14.1 +/- 3.3%/h, respectively). Neither unfractionated nor low molecular weight heparin significantly affected this increase. [131I]-Albumin clearance was significantly increased in diabetic rats in the eye, skin and skeletal muscle tissues compared with normal rats (0.17-0.40 vs 0.1-0.23 microL plasma/g per min). Low molecular weight heparin treatment did not affect the increased organ albumin clearance. 4. In conclusion, heparin treatment does not affect diabetes-induced vascular dysfunction as expressed by increased TERalb and clearance of albumin in rats.