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

Abstract

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 onmore » blood flow and vascular albumin permeation in some tissues suggest that increased vascular albumin permeation is not entirely attributable to hemodynamic change.« less

Authors:
; ; ; ; ; ; ;  [1]
  1. Washington Univ. School of Medicine, St. Louis, MO (USA)
Publication Date:
OSTI Identifier:
5225476
Resource Type:
Journal Article
Journal Name:
Diabetes; (USA)
Additional Journal Information:
Journal Volume: 38:10; Journal ID: ISSN 0012-1797
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; DIABETES MELLITUS; PATHOGENESIS; ENZYME INHIBITORS; BIOLOGICAL FUNCTIONS; GLUCOSE; METABOLISM; ALBUMINS; BLOOD FLOW; CATTLE; COBALT 57; EDTA; IODINE 125; MICROSPHERES; OXIDOREDUCTASES; RATS; STRONTIUM 85; TRACER TECHNIQUES; ALDEHYDES; ALKALINE EARTH ISOTOPES; AMINO ACIDS; ANIMALS; BETA DECAY RADIOISOTOPES; CARBOHYDRATES; CARBOXYLIC ACIDS; CHELATING AGENTS; COBALT ISOTOPES; DAYS LIVING RADIOISOTOPES; DISEASES; DOMESTIC ANIMALS; ELECTRON CAPTURE RADIOISOTOPES; ENDOCRINE DISEASES; ENZYMES; EVEN-ODD NUCLEI; FUNCTIONS; HEXOSES; HOURS LIVING RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOMERIC TRANSITION ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; MAMMALS; METABOLIC DISEASES; MONOSACCHARIDES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; PROTEINS; RADIOISOTOPES; RODENTS; RUMINANTS; SACCHARIDES; STRONTIUM ISOTOPES; VERTEBRATES; 550901* - Pathology- Tracer Techniques

Citation Formats

Tilton, R G, Chang, K, Pugliese, G, Eades, D M, Province, M A, Sherman, W R, Kilo, C, and Williamson, J R. Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. United States: N. p., 1989. Web. doi:10.2337/diabetes.38.10.1258.
Tilton, R G, Chang, K, Pugliese, G, Eades, D M, Province, M A, Sherman, W R, Kilo, C, & Williamson, J R. Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. United States. https://doi.org/10.2337/diabetes.38.10.1258
Tilton, R G, Chang, K, Pugliese, G, Eades, D M, Province, M A, Sherman, W R, Kilo, C, and Williamson, J R. 1989. "Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors". United States. https://doi.org/10.2337/diabetes.38.10.1258.
@article{osti_5225476,
title = {Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors},
author = {Tilton, R G and Chang, K and Pugliese, G and Eades, D M and Province, M A and Sherman, W R and Kilo, C and Williamson, J R},
abstractNote = {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.},
doi = {10.2337/diabetes.38.10.1258},
url = {https://www.osti.gov/biblio/5225476}, journal = {Diabetes; (USA)},
issn = {0012-1797},
number = ,
volume = 38:10,
place = {United States},
year = {Sun Oct 01 00:00:00 EDT 1989},
month = {Sun Oct 01 00:00:00 EDT 1989}
}