Prevention of albuminuria by captopril in diabetic rats.
1. Streptozotocin diabetic rats were treated with captopril (50 mg l), an angiotensin converting enzyme-inhibitor, in drinking water for 20 weeks. 2. Systolic blood pressure and 24-hr urinary excretions of heparan sulfate and albumin were done at 2, 8, 16 and 20 weeks. 3. At the end of 20 weeks, all rats were killed, kidneys removed and glomeruli isolated. 4. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of 35S-sulfate. 5. Captopril significantly lowered blood pressure in diabetic rats 8 weeks after treatment. 6. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from nondiabetic rats. 7. Further characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. 8. Therapy with captopril normalized not only glomerular synthesis and content but also various fractions of heparan sulfate in diabetic rats. 9. Excretions of heparan sulfate and albumin were significantly higher in diabetic than in nondiabetic rats. 10. Captopril therapy did significantly lower but not normalize both these excretions in diabetic rats. 11. The data suggest that catopril therapy improves albuminuria through preservation of glomerular heparan sulfate and prevention of its urinary loss in diabetic rats.
Reddi
A S
AS
Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103.
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D002852:Chromatography, Ion Exchange; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000652:urine; D006025:Glycosaminoglycans / Q000096:biosynthesis / Q000378:metabolism; D006493:Heparin / Q000096:biosynthesis / Q000652:urine; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes
D001786:Blood Glucose; D006025:Glycosaminoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; C020341:glucosaminoglycans; D006493:Heparin; D002216:Captopril; D011188:Potassium