Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors

Journal Article · Sun Oct 01 04:00:00 EDT 1989 · Diabetes; (USA)

DOI:https://doi.org/10.2337/diabetes.38.10.1258· OSTI ID:5225476

Tilton, R G; Chang, K; Pugliese, G; Eades, D M; Province, M A; Sherman, W R; Kilo, C; Williamson, J R ^[1]

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1. Washington Univ. School of Medicine, St. Louis, MO (USA)

This study investigated hemodynamic changes in diabetic rats and their relationship to changes in vascular albumin permeation and increased metabolism of glucose to sorbitol. The effects of 6 wk of streptozocin-induced diabetes and three structurally different inhibitors of aldose reductase were examined on (1) regional blood flow (assessed with 15-microns 85Sr-labeled microspheres) and vascular permeation by 125I-labeled bovine serum albumin (BSA) and (2) glomerular filtration rate (assessed by plasma clearance of 57Co-labeled EDTA) and urinary albumin excretion (determined by radial immunodiffusion assay). In diabetic rats, blood flow was significantly increased in ocular tissues (anterior uvea, posterior uvea, retina, and optic nerve), sciatic nerve, kidney, new granulation tissue, cecum, and brain. 125I-BSA permeation was increased in all of these tissues except brain. Glomerular filtration rate and 24-h urinary albumin excretion were increased 2- and 29-fold, respectively, in diabetic rats. All three aldose reductase inhibitors completely prevented or markedly reduced these hemodynamic and vascular filtration changes and increases in tissue sorbitol levels in the anterior uvea, posterior uvea, retina, sciatic nerve, and granulation tissue. These observations indicate that early diabetes-induced hemodynamic changes and increased vascular albumin permeation and urinary albumin excretion are aldose reductase-linked phenomena. Discordant effects of aldose reductase inhibitors on blood flow and vascular albumin permeation in some tissues suggest that increased vascular albumin permeation is not entirely attributable to hemodynamic change.

• OSTI ID: 5225476
• Journal Information: Diabetes; (USA), Journal Name: Diabetes; (USA) Vol. 38:10; ISSN 0012-1797; ISSN DIAEA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ALDEHYDES
ALKALINE EARTH ISOTOPES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BLOOD FLOW
CARBOHYDRATES
CARBOXYLIC ACIDS
CATTLE
CHELATING AGENTS
COBALT 57
COBALT ISOTOPES
DAYS LIVING RADIOISOTOPES
DIABETES MELLITUS
DISEASES
DOMESTIC ANIMALS
EDTA
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
ENZYME INHIBITORS
ENZYMES
EVEN-ODD NUCLEI
FUNCTIONS
GLUCOSE
HEXOSES
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METABOLIC DISEASES
METABOLISM
MICROSPHERES
MONOSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATHOGENESIS
PROTEINS
RADIOISOTOPES
RATS
RODENTS
RUMINANTS
SACCHARIDES
STRONTIUM 85
STRONTIUM ISOTOPES
TRACER TECHNIQUES
VERTEBRATES