Interaction of phosphodiesterase inhibitors triamterene, papaverine, theophylline, IBMX and amrinone with other positive inotropic acting substances on isolated guinea-pig atria.

On isolated electrically stimulated left and spontaneously beating right guinea-pig atria the interaction between PDE-inhibitors and the positive inotropic and chronotropic action of orciprenaline, forskolin and histamine in dose-response curve was examined. The experiments led to the following results: triamterene (20-120 mumol/l) and papaverine (10-100 mumol/l) inhibit the positive inotropic and chronotropic action of orciprenaline, whereas theophylline (10-100 mumol/l) and isobutyl-methyl-xanthine (0.1-10 mumol/l) only inhibit the inotropic action of orciprenaline. Amrinone (100-316 mumol/l) increases the positive inotropic and chronotropic action of orciprenaline; the positive inotropic and chronotropic action of forskolin is inhibited by triamterene but not by theophylline and IBMX. The positive chronotropic action of forskolin and histamine is inhibited by triamterene, whereas the positive inotropic action of histamine is not influenced; our experimental results suggest that triamterene and papaverine antagonize orciprenaline action by inhibition of adenylate cyclase. For this there is further evidence in the antagonism between triamterene and the inotropic action of forskolin and the tachycardic action of histamine. As theophylline and IBMX inhibit only the inotropic action of orciprenaline, there might be a different mechanism for their interaction regarding the chronotropic action of orciprenaline compared to triamterene and papaverine. The amrinone mechanism differs from that of the other PDE-inhibitors as it increases the positive inotropic and chronotropic action of orciprenaline.