MEDIATOR-INDUCED CHANGES IN MACROMOLECULAR PERMEABILITY IN THE RAT MESENTERIC MICROCIRCULATION

An intravital fluorescence microscopic method for measurement of changes in macromolecular permeability has been established in the mesenterial microcirculation of the rat. After exteriorization of the fat-free distal part of the ileal mesentery, a 1-hr period of stabilization was followed by the injection of FITC-labeled macromolecules. Five minutes later, histamine, leukotriene B-4, or leukotriene C-4 was topically applied to the tissue by means of a micromanipulator. Areas of 1 mm(2) were videotaped with a SIT camera. The fluorescence intensity of these areas was measured by an analogous video image processing system and displayed as gray value histograms. The shift of the frequency of gray levels from lower to upper regions could be attributed to an increase in light intensity in the mesentery, indicating an increase in vessel wall permeability. The sites of action of histamine and leukotriene C-4 were very similar. Both mediators affected mainly the larger collecting venules, In contrast, leukotriene Bq exerted its effect at postcapillary venules. Moreover, leukotriene B-4-induced extravasation was inhibited by superoxide dismutase, suggesting an involvement of oxygen radicals. The studies with histamine alone and with H-1- and H-2-antagonists demonstrated that histamine-induced extravasation in the rat mesentery was mediated by H-1-histamine receptors. The present study introduces an experimental model for the measurement of changes in macromolecular permeability, which is useful for studying mediator effects and their pharmacological inhibition in the microcirculation of the rat mesentery. (C) 1995 Academic Press, Inc.