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

Ronald Tilton, K. Chang, G. Pugliese, D. M. Eades, M. A. Province, W. R. Sherman, C. Kilo, J. R. Williamson

Research output: Contribution to journalArticle

172 Citations (Scopus)

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-μm 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 changes. We hypothesize that 1) increases in blood flow may reflect impaired contractile function of smooth muscle cells in resistance arterioles and 2) increases in vascular 125I-BSA permeation and urinary albumin excretion reflect impaired vascular barrier functional integrity in addition to increased hydraulic conductance secondary to microvascular hypertension associated with decreased vascular resistance.

Original languageEnglish (US)
Pages (from-to)1258-1270
Number of pages13
JournalDiabetes
Volume38
Issue number10
StatePublished - 1989
Externally publishedYes

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Aldehyde Reductase
Blood Vessels
Albumins
Hemodynamics
Uvea
Bovine Serum Albumin
Granulation Tissue
Sorbitol
Sciatic Nerve
Glomerular Filtration Rate
Retina
Nerve Tissue
Experimental Diabetes Mellitus
Cecum
Immunodiffusion
Regional Blood Flow
Brain
Arterioles
Optic Nerve
Microspheres

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Tilton, R., Chang, K., Pugliese, G., Eades, D. M., Province, M. A., Sherman, W. R., ... Williamson, J. R. (1989). Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes, 38(10), 1258-1270.

Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. / Tilton, Ronald; Chang, K.; Pugliese, G.; Eades, D. M.; Province, M. A.; Sherman, W. R.; Kilo, C.; Williamson, J. R.

In: Diabetes, Vol. 38, No. 10, 1989, p. 1258-1270.

Research output: Contribution to journalArticle

Tilton, R, Chang, K, Pugliese, G, Eades, DM, Province, MA, Sherman, WR, Kilo, C & Williamson, JR 1989, 'Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors', Diabetes, vol. 38, no. 10, pp. 1258-1270.
Tilton R, Chang K, Pugliese G, Eades DM, Province MA, Sherman WR et al. Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes. 1989;38(10):1258-1270.
Tilton, Ronald ; 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. In: Diabetes. 1989 ; Vol. 38, No. 10. pp. 1258-1270.
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