Superoxide dismutase restores impaired histamine-induced increases in venular macromolecular efflux during diabetes mellitus

William G. Mayhan, Glenda M. Sharpe

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The goal of this study was to determine the role of oxygen radicals in impaired histamine-induced increases in venular macromolecular efflux from the hamster cheek pouch. We used intravital fluorescent microscopy and fluorescent isothiocyanate dextran (FITC-dextran; MW = 70K) to examine macromolecular extravasation from post-capillary venules in nondiabetic and diabetic (2-4 weeks after injection of streptozotoein) hamsters in response histamine. Increases in extravasation of macromolecules were quantitated by counting venular leaky sites and by calculating clearance (ml/s x 10-6) of FITC-dextran-70K. In nondiabetic hamsters, supervision with histamine (1.0 and 5.0 μM) increased venular leaky sites from 0 ± 0 to 17 ±6 and 35 ± 6 per 0.11 cm2, respectively. In addition, clearance of FITC-dextran-70K increased during superfusion with histamine. In contrast, supervision with histamine did not increase the formation of venular leaky sites (0 ± 0) or clearance of FITC-dextran-70K in diabetic hamsters. Next, we examined whether alterations in histamine-induced increases in macromolecular efflux in diabetic hamsters may be related to the production of oxygen radicals. We examined whether exogenous application of superoxide dismutase (150 U/ml) could restore impaired histamine-induced increases in macromolecular extravasation in diabetic hamsters. Application of superoxide dismutase did not alter histamine-induced increases in venular leaky sites or clearance of FITC-dextran-70K in nondiabetic hamsters. However, application of superoxide dismutase restored histamine-induced increases in leaky site formation and clearance of FITC-dextran-70K in diabetic hamsters towards that observed in nondiabetic hamsters. These findings suggest that oxygen radical formation appears to contribute to impaired macromolecular efflux in response to histamine during short-term diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalMicrocirculation
Volume5
Issue number2-3
Publication statusPublished - Dec 1 1998

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Keywords

  • Nitric oxide
  • Oxygen radicals
  • Permeability
  • Venules

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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