Effects of catecholamine uptake inhibitors on the positive inotropic responses to isoprenaline, dobutamine and dopexamine in human, rat and guinea-pig atrial heart muscle.

The inotropic effects of isoprenaline, dobutamine and dopexamine were studied in human right atrial myocardium and in rat and guinea-pig left atria electrically stimulated at 1 Hz. To investigate the contribution of endogenously released catecholamines to the positive inotropic effects of beta-adrenoceptor agonists, experiments were performed both in the absence and in the presence of the uptake inhibitors desipramine and corticosterone. In all three species, the maximum positive inotropic responses to isoprenaline and dobutamine were not influenced by the pretreatment, whereas the responses to dopexamine were modified, i.e. the maximum force increase was reduced and the concentration-response curves were shifted to the right. After uptake inhibition, the decrease in positive inotropic action of dopexamine was largest in rat atria followed by guinea-pig and human atria. It is concluded that, in the untreated atrial muscle from all three species, endogenous catecholamines contribute only to the inotropic responses of dopexamine but not to those of isoprenaline or dobutamine.