In rats under either mild stress (= controls) or severe stress (= restraint) gastric secretion (acid; pepsin, volume), mucosal blood flow, serum gastrin and ulcer formation were evaluated without and with additional infusion of a low dose (0.25 mg/kg.h) metiamide over an 8 h experimental period. Calculated constants of dose-response characteristics for acid output in this species are: Km = 1.41 +/- 0.36 mg/kg.h; Vmax = 94.4 +/- 11.0 per cent. Restraint depresses markedly secretion and microcirculation, but stimulates ulcer formation and raises serum gastrin. In controls, metiamide inhibits secretion and ulcer index significantly, but leaves mucosal blood flow and gastrin unaltered. In contrast, with restraint and metiamide, ulcer index was not improved, whereas mucosal blood flow was restored to almost control levels. Therefore, H2-receptor blockers, in addition to inhibition of secretion, may interfere with microcirculation either directly or by secondary release of yet unknown mediator substance(s), depending on the prevailing tissue environment.
Acids Animals