| Enalapril improves albuminuria by preventing glomerular loss of heparan sulfate in diabetic rats. | |
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MedLine Citation:
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PMID: 2015105 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Angiotensin converting enzyme (ACE) inhibitors, particularly enalapril and captopril, have been shown to decrease proteinuria in diabetic animals and human subjects. Since heparan sulfate proteoglycan confers a negative charge on the glomerular basement membrane, and either decreased synthesis or loss of this charge causes albuminuria in diabetic animals, we examined the possibility that enalapril prevents albuminuria through glomerular preservation of heparan sulfate in long-term diabetic rats. A total of 22 male Wistar rats were used in the study. Diabetes was induced in 15 rats by a single intraperitoneal injection of streptozotocin (60 mg/kg). The remaining 7 rats received buffer. One week following induction of diabetes, 8 diabetic rats were allowed to drink tap water containing enalapril at a concentration of 50 mg/liter; the remaining 7 diabetic and 7 nondiabetic rats were given only tap water. The drug treatment was continued for 20 weeks. Systolic blood pressure and 24-hr urinary excretion of albumin were measured at 2, 8, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated by differential sieving technique. Total glycosaminoglycan and heparan sulfate synthesis was determined by incubating glomeruli in the presence of [35S]sulfate. Characterization of heparan sulfate was performed by ion-exchange chromatography. Systolic blood pressures were significantly lower in enalapril-treated diabetic rats compared to untreated diabetic rats. Diabetic glomeruli synthesized less heparan sulfate than glomeruli from nondiabetic rats. Also, glomerular heparan sulfate content of diabetics was significantly lower than that of nondiabetics. Further characterization of heparan sulfate 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. Enalapril treatment normalized not only glomerular synthesis and content but also various fractions of heparan sulfate in diabetic rats. Diabetic rats excreted increased quantities of heparan sulfate and albumin than nondiabetic rats. Enalapril therapy prevented both these increases in diabetic rats. These data suggest that enalapril treatment improves albuminuria through preservation of glomerular heparan sulfate and prevention of its urinary loss in diabetic rats. |
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Authors:
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A S Reddi; R Ramamurthi; M Miller; S Dhuper; N Lasker |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical medicine and metabolic biology Volume: 45 ISSN: 0885-4505 ISO Abbreviation: Biochem. Med. Metab. Biol. Publication Date: 1991 Feb |
Date Detail:
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Created Date: 1991-05-20 Completed Date: 1991-05-20 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8605718 Medline TA: Biochem Med Metab Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 119-31 Citation Subset: IM |
Affiliation:
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Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103-2757. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Albuminuria
/
complications,
drug therapy*,
metabolism Animals Basement Membrane / metabolism Diabetic Nephropathies / complications, drug therapy*, metabolism Enalapril / pharmacology* Glycosaminoglycans / metabolism Heparitin Sulfate / metabolism*, urine Kidney Glomerulus / drug effects, metabolism Male Rats Rats, Inbred Strains |
| Chemical | |
Reg. No./Substance:
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0/Glycosaminoglycans; 75847-73-3/Enalapril; 9050-30-0/Heparitin Sulfate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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