The effect of antihistamines and indomethacin on microvascular permeability changes due to repeated pressure-induced local ischemia.

Indomethacin can reduce the microvascular permeability induced by repeated ischemia. In this investigation the influence of histamine H1 and H2 receptor blockers was studied for comparison with indomethacin. Application of 60 mmHg pressure to the hamster cheek pouch for 5 min was repeated eight times, with 10-min restitution intervals. Altered permeability was evaluated with use of FITC-dextran and intravital microscopy. Progressive efflux of FITC-dextran was observed in the control group. When either diphenhydramine or indomethacin was used alone, a few spots of extravasated dye were seen. Combination of diphenhydramine with either indomethacin or cimetidine reduced the extravasation. Furthermore, the spots appeared significantly later than in the controls, and some faded. Increase in the efflux of macromolecules due to repeated ischemia seems to be mediated via H1 and H2 receptors in conjunction with other receptors and/or amines e.g. prostaglandins.