ACID SECRETORY AND DUODENAL ULCEROGENIC RESPONSES INDUCED BY MEPIRIZOLE IN ANESTHETIZED RATS - RELATION TO BODY-TEMPERATURE

The role of body temperature in the acid stimulatory mechanism by mepi rizole, a duodenal ulcerogen, was investigated in urethane-anesthetize d rats. Subcutaneous administration of mepirizole (60 and 200 mg/kg) i ncreased acid secretion in a dose-dependent manner and resulted in duo denal lesions within 8 hr. The acid secretory and ulcerogenic response s induced by mepirizole were inhibited completely by vagotomy and sign ificantly reduced by subcutaneous pretreatment with atropine (1 mg/kg) , hexamethonium (10 mg/kg), or clonidine (1 mg/kg). During anesthesia, body temperature was decreased to 34 degrees C in control rats but fu rther reduced to 31 degrees C after administration of mepirizole. When body temperature was maintained at 36 degrees C during a test period, mepirizole caused significantly less effect on acid secretion and pro duced less damage in the duodenum. In addition, intracisternal adminis tration of antiserum of thyrotropin-releasing hormone (TRH: 5 mu 1/rat ) also significantly inhibited acid hypersecretion and development of duodenal lesions in response to mepirizole. When acid output induced b y mepirizole was plotted against duodenal lesion score from one group to another, a significant linear relationship was found between these two values (r = 0.814, P < 0.05). We conclude that mepirizole induced vagally mediated acid secretion and duodenal lesions in anesthetized r ats. These responses may occur centrally in association with lowering of body temperature, which potentiates the acid stimulatory effect of mepirizole, probably through a TRH-dependent mechanism.