INOTROPIC AND CHRONOTROPIC EFFECTS OF DICHLOROISOPROTERENOL ON RAT ATRIA

¹ Departments of Pharmacology, Schools of the Health Professions, University of Pittsburgh, Pittsburgh, Pennsylvania

Dichloroisoproterenol, in concentrations of 5 x 10^-8 to 5 x 10^-6 g/ml, had properties of a sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. These effects were long lasting and could not be terminated by repeated washing, and further exposure of the tissue to DCI elicited reduced responses. In reserpinized atria, the positive inotropic action of DCI was abolished while its chronotropic action was markedly reduced. Repletion of norepinephrine stores in reserpinized atrial preparations made the tissue responsive to the action of DCI. The incubation of reserpinized atria with norepinephrine in the presence of DCI, or of normal atria with norepinephrine after exposure to DCI, failed to restore the augmentory action of DCI. Treatment of atria with cocaine, DCI, nethalide, bretylium, guanethidine, and isoproterenol either reduced, abolished, or reversed the positive chronotropic and inotropic actions of DCI. It is concluded that sympathomimetic effects of low concentrations of DCI are mainly elicited through its action on the stores of norepinephrine in the atrial tissue and are mediated through the stimulation of -adrenergic receptors.

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