The positive inotropic action of the nifedipine analogue, Bay K 8644, in guinea‐pig and rat isolated cardiac preparations

Abstract

1 The inotropic effect of Bay K 8644 has been studied in rat and guinea-pig atria and ventricular strips stimulated at 1 Hz, in a medium containing CaCl₂ 1.8 mM. The positive inotropic effect at maximal effective concentrations of Bay K 8644 was in the following order: guinea-pig ventricle > rat ventricle > guinea-pig atria >> rat atria. 2 In rat preparations, the tension recorded at maximum effective concentrations of Bay K 8644 was similar at three different calcium concentrations (0.7, 1.8, 3.0 mM). The amplitude of the positive inotropic effect evoked by Bay K 8644 increased when atrial and ventricular contractions were reduced by lowering the external calcium concentration. 3 The contractile tension reached in the presence of maximum effective concentrations of Bay K 8644 (3 × 10⁻⁷ − 1 × 10⁻⁶ M) was greater than that produced by the maximum effective concentration of external calcium (3 mM) in rat ventricles but not in rat atria. 4 High doses of nifedipine (3 × 10⁻⁷ − 1 × 10⁻⁶ M) depressed the contraction of rat atria more than the contraction of rat ventricles. 5 In rat ventricles, nifedipine shifted to the right the inotropic dose-effect curve of Bay K 8644. 6 It is concluded that the interaction between nifedipine and Bay K 8644 occurred at the same binding sites. These sites have some characteristics of the low affinity binding sites of nifedipine and other related dihydropyridines.