CIRCADIAN REACTIVITY RHYTHM OF RAT GASTRIC-MUCOSA TO RESTRAINT-COLD STRESS AND INDOMETHACIN - TEMPORAL VARIATION IN THE PROTECTIVE EFFECT OF ILOPROST

In this study, the time-dependent ulcerogenic effects of restraint-old stress and indomethacin on the gastric mucosa and the temporal variat ion in the protective effect of iloprost, a synthetic stable analog of prostacyclin, were investigated in rats synchronized to 12h light and 12h darkness, lights on at 08:00. The severity of gastric ulceration produced by either stress or indomethacin showed marked circadian vari ation; it was greatest at 11 HALO (hours after lights on) for restrain t-cold stress and at 23 HALO for indomethacin. The severity of the ind uced ulcerogenesis was least at 7 HALO for both stimuli. The protectiv e effect of iloprost against restraint-cold stress was most prominent at 15 HALO and 19 HALO with an approximately 80% protection score. On the other hand, pretreatment with iloprost reduced the indomethacin-in duced mucosal injury only at 23 HALO. The circadian variation in the e ffect of iloprost and in the rhythmic modalities of these two experime ntal ulcer models are indicative of differences in their underlying me chanisms. In experimental models of ulceration, the circadian time of application of the ulcerogenic stimulus must be considered as an impor tant experimental factor. Moreover, the protective effectiveness of an tiulcer drugs can express time-dependent differences and must also be taken into account in investigative research.