Superoxide dismutase restores impaired histamine-induced increases in venular macromolecular efflux during diabetes mellitus.
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 isothiocyanate dextran (FITC-dextran; MW = 70K) to examine macromolecular extravasation from post-capillary venules in nondiabetic and diabetic (2-4 weeks after injection of streptozotocin) hamsters in response to 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, superfusion with histamine (1.0 and 5.0 microM) 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, superfusion 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.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Sharpe
G M
GM
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D003911:Dextrans / Q000493:pharmacokinetics; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005609:Free Radicals / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D046911:Macromolecular Substances; D008647:Mesocricetus; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014699:Venules / Q000187:drug effects* / Q000378:metabolism*
D003911:Dextrans; D005609:Free Radicals; D046911:Macromolecular Substances; D017382:Reactive Oxygen Species; C015219:fluorescein isothiocyanate dextran; D006632:Histamine; D013482:Superoxide Dismutase; D016650:Fluorescein-5-isothiocyanate