Generation of superoxide anion impairs histamine-induced increases in macromolecular efflux

The first goal of this study was to determine the effect of generation of superoxide anion using pyrogallol on histamine-induced increases in macromolecular efflux. We used intravital microscopy and fluorescein isothiocyanate-dextran (FITC-dextran; MW 70K) to examine macromolecular extravazation from postcapillary venules in the hamster cheek pouch in response to histamine before and following topical application of vehicle or pyrogallol. Extravazation of macromolecules was quantitated by counting venular leaky sites. Histamine elicited reproducible increases in venular leaky sites before and during infusion of vehicle. In contrast, topical application of pyrogallol (0.5 mM) abolished histamine-induced increases in formation of venular leaky sites. Our second goal was to examine whether pyrogallol-induced inhibition of venular leaky site formation could be reversed by superoxide dismutase. Application of superoxide dismutase (300 U/ml) to the cheek pouch in the presence of pyrogallol restored histamine-induced increases in venular leaky sites. Thus, the generation of superoxide anion alters histamine-induced increases in macromolecular efflux. These results support the concept that disease states that produce oxidative stress may impair agonist-induced increases in microvascular permeability via inactivation of nitric oxide.