On the action of nifedipine under conditions of variable stimulation patterns and [Ca2+]0 in guinea-pig atrium

The effect of nifedipine is studied in perfused isolated guinea-pig left atrium at a temperature of 37 degrees C and a stimulation rate between 60 and 240/min. Rhythmical stimulation at 240/min was interrupted by interposed stimulus intervals (test intervals) in a range of 0.1-4 s. The pressure amplitudes developed during subsequent test contractions rise up to a maximum with increasing test intervals. This time course is described as restitution in contractile response. Results. Restitution is somewhat faster in earlier than in later stages of perfusion. A rise in [Ca2+]0 accelerates restitution without changing maximal pressure development. Lowering [Ca2+]0 depresses pressure amplitudes over the whole range of test intervals. Nifedipine slows down restitution but has (in concentrations up to 10(-6) M) no effect on the maximum achieved after long test intervals following stimulation at 240/min. The negative inotropic effect of nifedipine on rhythmical pressure development rises with increasing stimulation frequency in the range from 60-240/min. An elevation in [Ca2+]0 does not reestablish control pressure-frequency relationship. Conclusions. In respect to the restitution process and also to the pressure-frequency relationship the effect of nifedipine can neither be simulated by a reduction in [Ca2+]0 nor abolished by an elevation in [Ca2+]0.