Comparison of angiotensin converting enzyme inhibitors captopril and MK421-diacid in guinea pig atria.

Angiotensin I (AI) and angiotensin II (AII) caused concentration-dependent increases in atrial rate in guinea pig isolated right atria. Converting enzyme inhibitors captopril and MK421-diacid did not alter the responses to AII but displaced the curves to AI to the right. The atrial response to generated AII from AI was used as a bioassay to estimate the dissociation constants of converting enzyme inhibitors (Kb) and test for kinetics of simple competition. MK421-diacid was 12-40 times more potent than captopril. However, estimations of Kb for captopril and MK421-diacid were unsatisfactory because at high concentrations of inhibitors the curves to AI were not displaced according to simple competition. We conclude that AI in high concentration can stimulate AII receptors accounting for the stationary displacement of curves to AI in the presence of converting enzyme inhibitors. MK421-diacid also potentiates responses to bradykinin in this assay.