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Superoxide Dismutase Restores Impaired Histamine‐Induced Increase in Venular Macromolecular Efflux During Diabetes Mellitus
Author(s) -
MAYHAN WILLIAM G.,
SHARPE GLENDA M.
Publication year - 1998
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.1998.tb00070.x
Subject(s) - superoxide dismutase , histamine , diabetes mellitus , efflux , chemistry , endocrinology , medicine , pharmacology , biochemistry , oxidative stress
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 fluorescein isothio‐cynate dextran (FITC‐dextran; MW = 70 K) to examine macromolecular extravasation from post‐capillary venules in nondiabetic and diabetic (2–4 weeks after injection of streptozoticin) hamsters in response to histamine. Increases in extravasation of macromolecules were quantitated by counting venular leaky sites and by calculating clearance (ml/s × 10 −6 ) of FITC‐dextran‐70 K. In non‐diabetic hamsters, superfusion with histamine (1.0 and 5.0 µM) increased venular leaky sites from 0 ± 0 to 17 ± 6 and 35 ± 6 per 0.11 cm 2 , respectively. In addition, clearance of FITC‐dextran‐70 K increased during superfusion with histamine. In contrast, superfusion with histamine did not increase the formation of venular leaky sites (0 ± 0) or clearance of FITC‐dextran‐70 K 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‐70 K in nondiabetic hamsters. However, application of superoxide dismutase restored histamine‐induced increases in leaky site formation and clearance of FITC‐dextran‐70 K 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.