EFFECTS OF CATECHOLAMINE UPTAKE INHIBITORS ON THE POSITIVE INOTROPIC RESPONSES TO ISOPRENALINE, DOBUTAMINE AND DOPEXAMINE IN HUMAN, RAT ANDGUINEA-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 lef t atria electrically stimulated at 1 Hz. To investigate the contributi on of endogenously released catecholamines to the positive inotropic e ffects of beta-adrenoceptor agonists, experiments were performed both in the absence and in the presence of the uptake inhibitors desipramin e and corticosterone. In all three species, the maximum positive inotr opic responses to isoprenaline and dobutamine were not influenced by t he pretreatment, whereas the responses to dopexamine were modified, i. e. the maximum force increase was reduced and the concentration-respon se curves were shifted to the right. After uptake inhibition, the decr ease in positive inotropic action of dopexamine was largest in rat atr ia followed by guinea-pig and human atria. It is concluded that, in th e untreated atrial muscle from all three species, endogenous catechola mines contribute only to the inotropic responses of dopexamine but not to those of isoprenaline or dobutamine.