INTERACTION BETWEEN NOREPINEPHRINE AND DICHLOROISOPROTERENOL DURING ADRENERGIC BLOCKADE OF THE ISOLATED PERFUSED RAT HEART

¹ Department of Pharmacology, Division of Basic Health Sciences, Emory University, Atlanta, Georgia

The present study is an examination of the hypothesis that norepinephrine (NE) and Dichloroisoproterenol (DCI) compete for the same receptor sites in the heart, and that this type of interaction can account for the surmountable adrenergic blockade produced by DCI. The problem was approached by examining (1) the effect of DCI on the uptake of NE, and (2) the effect of NE on the release of a prior dose of DCI. All experiments were performed on isolated, perfused hearts from normal or reserpine treated rats. Drug uptake and release was determined using H³-NE and H³-DCI.

H³-NE uptake was unaffected by pretreatment with DCI, regardless of the magnitude of blockade of contractile effects. Some doses of NE were shown to produce a greater release of H³-DCI than injection of a comparable volume of saline. When a series of NE injections was given, the first dose always produced a greater release of DCI than did subsequent doses; this response was unrelated to the degree of antagonism of the contractile effect. The magnitude of DCI release in response to the first dose of NE given after administration of DCI could not be correlated with size of dose over the full range of doses tested; this response was also unrelated to degree of blockade. Measurable displacement of DCI was shown to be unnecessary for restoration of physiological effect.

DCI uptake by the isolated hearts from reserpine pretreated rats was not different from the uptake by normal hearts. The release of DCI in response to NE given to reserpinized hearts followed the same pattern as shown in normal hearts.