The effects of the cardiotonic dihydropyridine derivatives Bay k 8644 and H160/51 on post-rest adaptation of guinea-pig papillary muscles

Abstract

In isolated guinea-pig papillary muscle, the effect of the two dihydropyridine derivatives Bay k 8644 (0.03-10 mumol/l) and H160/51 (0.1-3 mumol/l) on transmembrane action potentials and force of contraction were investigated at regular stimulation (1 Hz) and after a period of rest (10 min). The following results were obtained: At regular stimulation of the preparations, Bay k 8644 and H160/51 enhanced force of contraction without affecting time-to-peak tension. The time required for relaxation and the action potential duration were prolonged. These effects were transient with exposure to high concentrations of Bay k 8644 (greater than 3 mumol/l). The amplitude of the post-rest contraction thought to depend entirely on transmembrane calcium influx was small under control conditions and increased because of prolongation in time-to-peak tension in the presence of either dihydropyridine derivative. Isoprenaline (30 nmol/l) - as opposed to Bay k 8644 and H160/51 - increased the rate of force development of post-rest contractions. Bay k 8644 and H160/51 prolonged the duration of the first action potential after 10 min of rest. In the course of adaptation to steady state stimulation this prolongation transiently increased further resulting in a biphasic pattern which was attenuated by addition of nifedipine. With isoprenaline the biphasic pattern changed into a monotonous adaptation to pre-rest control. Our results show that the small enhancement of the post-rest contraction in the presence of Bay k 8644 or H160/51 is due to prolonged action potential duration after rest, whereas isoprenaline enhances the intensity of post-rest activation.(ABSTRACT TRUNCATED AT 250 WORDS)