Uterine vascular permeability changes, measured quantitatively by trypan blue accumulation, and measurements of uterine water content, were used to study the postulated role of histamine as a mediator of oestrogen action. Histamine (H), oestradiol (E), 1·3% NaCl solution, an antihistamine (AH—diphenhydramine hydrochloride—Benadryl) or xylene (X), was injected intraluminally into each uterine horn of ovariectomized rats. At intervals of 1/4–24 hr. after treatment uterine vascular changes were determined by comparing the trypan blue concentration of treated uteri with the concentration in ovariectomized controls. In the 1/4–1 hr. time periods 1·0 mg. H and 0·5–2·5 mg. AH showed increases 2 to 6 times greater than the slight permeability change induced by 0·04 μg. E or 1·3% NaCl, and were similar to that evoked by the inflammatory tissue irritant xylene. The characteristic uterine permeability effect of oestrogen was evident at 4 hr. at which time H and AH produced similar responses. However, histological examination showed a complete loss of epithelium of the uterine lumen caused by 1·0 mg. H, 0·5–2·5 mg. AH, and X during the first 4 hr. but only a partial loss with NaCl or E. When lower doses of histamine were administered, epithelial loss was reduced, and with 0·1 mg. histamine epithelial loss, uterine permeability, and water content approached those of rats treated with the 1·3% NaCl solution.
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