Aminoguanidine suppresses basal macromolecular extravasation during diabetes mellitus

William Mayhan, Glenda M. Sharpe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The goal of this study was to determine the effect of aminoguanidine on basal macromolecular efflux from the microcirculation of the hamster cheek pouch during diabetes mellitus. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextrans (FITC-dextran; mw = 70 and 20K) to examine basal macromolecular extravasation in nondiabetic hamsters, nondiabetic hamsters treated with a topical application of aminoguanidine (0.5 mM), diabetic hamsters (6-10 weeks after injection of streptozotocin), and diabetic hamsters treated with a topical application of aminoguanidine (0.5 mM). Increases in macromolecular efflux were quantitated by calculating the clearance (ml/s x 10-6) of FITC-dextran-70K and -20K. In nondiabetic hamsters, the clearance of FITC-dextran-70K and -20K remained relatively constant during the experimental period, although the clearance of FITC- dextran-70K was less than that for FITC-dextran-20K. Topical application of aminoguanidine did not alter basal permeability characteristics in nondiabetic hamsters. In diabetic hamsters, clearance of FITC-dextran-70K and -20K also remained relatively constant during the experimental period. However, the magnitude of clearance of FITC-dextran-70K and -20K was significantly greater in diabetic compared to nondiabetic hamsters (P < 0.05). Topical application of aminoguanidine restored basal permeability characteristics of diabetic hamsters to that observed in nondiabetic hamsters. These findings suggest that acute treatment of the microcirculation in vivo with aminoguanidine ameliorates basal increases in extravasation of macromolecules during diabetes mellitus. We suggest that aminoguanidine suppresses basal macromolecular efflux in diabetic hamsters via inhibition of nitric oxide synthase. Thus, it appears that the use of aminoguanidine may be an important therapeutic approach for the treatment of diabetes-related vascular dysfunction. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalMicrovascular Research
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2000

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Medical problems
Cricetinae
Diabetes Mellitus
Microcirculation
pimagedine
fluorescein isothiocyanate dextran
Permeability
Streptozocin
Macromolecules
Nitric Oxide Synthase
Microscopic examination
Cheek
Blood Vessels
Therapeutics

Keywords

  • Cheek pouch
  • FITC- dextran
  • Hamsters
  • In vivo microscopy
  • Nitric oxide
  • Permeability

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Aminoguanidine suppresses basal macromolecular extravasation during diabetes mellitus. / Mayhan, William; Sharpe, Glenda M.

In: Microvascular Research, Vol. 59, No. 1, 01.01.2000, p. 52-60.

Research output: Contribution to journalArticle

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