Effect of Histamine Receptor Antagonists and Indomethacin on Implantation in the Rabbit1

Anti-inflammatory drugs were given to pregnant rabbits during the 24-h period prior to the increase in the uterine vascular permeability which occurs on Day 7. Their effect on the vascular response was monitored by quantifying the concentration of extravascular Evans blue dye. The increase in vascular permeability normally seen on Day 7 was inhibited by either indomethacin or a combination of H1-(mepyramine) and H2-(cimetidine) receptor antagonists. When given alone, neither cimetidine nor mepyramine was as effective as the combination in reducing vascular permeability. Prostaglandins and histamine may be acting together since simultaneous administration of lower doses of indomethacin and the antihistamines reduced vascular permeability below that observed following administration of either class of anti-inflammatory drugs alone. In a second experiment, anti-inflammatory drugs were administered during the peri-implantation period (Days 6-8) and their effect on the weights of maternal and fetal tissues, and on fetal viability were evaluated on Day 14 of pregnancy. Indomethacin had a more deleterious effect on both parameters than did the combination of histamine receptor antagonists. Results from these experiments suggest that both prostaglandins and histamine may participate in the uterine vascular response, whereas the overall process of implantation appears to be more dependent upon the synthesis of prostaglandins than the action of histamine.