Changes in the ionic environment may alter the kind of antagonism of some histamine H2-receptor blockers in the guinea pig papillary muscle.

The effect of changes in the composition of the bathing medium on the effect of histamine and histamine H2-receptor antagonists was investigated in the isolated guinea pig papillary muscle. Ringer or Krebs-Henseleit solutions were used as nutrient fluids. They mainly differed with respect to pH and to Mg2+ and H2 PO4- content. Whereas the effect of histamine was not altered by ionic changes, the antagonism by some H2 blockers was different in the two nutrient solutions. The insurmountable antagonism elicited by high concentrations (greater than or equal to 10(-6) M) of famotidine, oxmetidine and mifentidine in Ringer solution was converted to surmountable when these drugs were tested in Krebs-Henseleit solution. Conversely, the antagonism induced by ranitidine was surmountable in both solutions, and that induced by high amounts of Ioxtidine was insurmountable in both nutrient fluids. Results obtained in Ringer solution were not modified by pH adjustments or by the addition of ions present in Krebs-Henseleit medium. These results suggest that the interaction of histamine with H2 receptors in the guinea pig papillary muscle was not influenced by alterations in the ionic composition of the nutrient fluid, whereas the antagonism may be critically dependent on the ionic environment.