Adrenaline, DB-c-AMP and myocardial ⁴⁵Ca exchange. Comparative studies in rat and guinea-pig auricles

Summary

The positive inotropic effect of adrenaline has been assumed to result from an increase in the intracellular level of c-AMP which, in turn, might enhance the permeability of the cardiac cell membrane to Ca²⁺. In order to further test this hypothesis, the effects of cyclic N⁶-2′-O-dibutyryl-adenosine-3′,5′-monophosphate (DB-c-AMP; 10⁻³ M) on mechanical performance, ⁴⁵Ca uptake and total tissue calcium concentration were investigated in electrically stimulated (120 beats/min) left auricles isolated from female rats weighing 180–220 g. The experiments were performed in Tyrode solution containing 0.9 mM CaCl₂; the duration of ⁴⁵Ca exposure was 3–60 min. In this study, DB-c-AMP markedly enhanced contractile force but the drug failed to detectably increase ⁴⁵Ca exchange (Figs. 1 and 2). This finding seemed to indicate that the effects of DB-c-AMP on myocardial ⁴⁵Ca exchange were completely different from those of adrenaline which previously (and in this study; Fig. 4) has been shown to accelerate ⁴⁵Ca exchange in auricles obtained from guinea-pigs of “normal” size. However, under the conditions used, adrenaline (2.2–5.5×10⁻⁶ M) also failed to significantly enhance ⁴⁵Ca exchange not only in rat auricles (Fig. 3) but also in small auricles isolated from very light guinea-pigs (body-weight 75–150 g; Fig. 4). From these findings it is concluded that druginduced changes in membrane calcium fluxes, which possibly occur, only might have escaped detection under the present experimental conditions. The “pool saturation phenomenon” previously described by Grossman and Furchgott (1964b; 1964c) is discussed to be the underlying mechanism. Thus, substantial conclusions on the effects of DB-c-AMP on myocardial Ca fluxes can as yet not be drawn. They must await experiments in which an adrenaline induced increase in cardiac ⁴⁵Ca exchange becomes detectable.