Stimulatory effects of DB-c-AMP and adrenaline on myocardial contraction and ⁴⁵Ca exchange. Experiments at reduced calcium concentration and low frequencies of stimulation

Summary

The effects of adrenaline (2.2×10⁻⁶ M) and 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 left auricles isolated from female rats weighing 180–220 g. The experiments were performed at reduced [Ca]_e of 0.45 mM and at various frequencies of stimulation (0–120 beats/min). In the first series of experiments ⁴⁵Ca incubation time was 5 min. Under these conditions DB-c-AMP as well as adrenaline enhanced contractile force to 300–450% of the control values at all frequencies tested (Fig.1). This increase in contractile force was accompanied by a significant enhancement in ⁴⁵Ca exchange (Fig.2) while the total tissue calcium concentration remained unchanged (Table 1). In resting auricles ⁴⁵Ca exchange was not altered under the influence of both drugs.

At long periods of ⁴⁵Ca exposure (40–90 min) both drugs augmented contractile force in a way similar to that of the first series of experiments (Fig.4) but no influence of DB-c-AMP or adrenaline on ⁴⁵Ca exchange could be detected (Fig.3).

It is concluded that DB-c-AMP can mimic the wellknown effects of adrenaline on myocardial calcium movements. Under the assumption that DB-c-AMP is representative for c-AMP, the results thus provide experimental support for the view that the positive inotropic effect of adrenaline is mediated by primary changes in the intracellular level of c-AMP which secondarily might enhance calcium fluxes across the cardiac cell membrane.