Inhibition of histamine-induced protein leakage in rat skeletal muscle by blockade of prostaglandin synthesis.

The effects of two prostaglandin synthesis blockers, indomethacin and mefenemic acid, on both histamine-induced extravasation of albumin and arteriole dilation were studied using intravital fluorescent microscopy. Sprague-Dawley rats (140-180 g) were anesthetized with pentobarbital (50mg/Kg) and the cremaster muscle was positioned in a Krebs bath (pH = 7.4, PCO2 = 40 mm Hg, PO2 = 35 mm Hg, temp = 34 degrees). Fluorescein isothiocyanate-labeled albumin was injected intravascularly and the fluorescent image of the cremaster microcirculation was produced by illumination from an argon laser (488 nm). Videotape analysis of the experiments showed that increasing concentrations of histamine in the bath produced both a concentration-dependent arteriole dilation and a concentration-dependent leakage of labeled albumin into the interstitium. Adding indomethacin (10 or 100 micrograms/ml) or mefenemic acid (10 micrograms/ml) to the Krebs bath significantly diminished the protein leakage induced by histamine but did not alter the arteriole dilation. These results indicate that prostaglandins may be directly involved in the histamine-induced increase in vascular permeability to macromolecules but not in the arteriole dilation histamine produces.