Circulating calcium modulates adrenaline induced cyclic adenosine monophosphate production

Inotropic support of the failing myocardium may combine calcium with adrenaline in an attempt to augment the haemodynamic actions of each drug. We have previously shown, however, that calcium blunts adrenaline induced increases in blood pressure and cardiac output in animals and man. The mechanisms by which calcium may interfere with the haemodynamic actions of adrenaline are not well understood. Adrenaline is known to stimulate adenylate cyclase and increase levels of cellular cyclic adenosine monophosphate (cAMP), a crucial second messenger in cell regulation. We evaluated the effect of increased circulating calcium levels on adrenaline stimulated cAMP production in laboratory animals. Calcium infusion in rats nearly doubled the circulating ionised calcium concentration, from 1.27 (SEM 0.03) mM to 2.3(0.18) mM. Adrenaline infusion significantly increased plasma cAMP in saline infused control animals, from 26(6) pmol·ml^-1 to 98(22) pmol·ml^-1, whereas there was no increase in cAMP plasma levels in the calcium infused rats. The apparent inhibition of adenylate cyclase by calcium may participate in a negative feedback system which helps protect cells from harmful intracellular calcium overload.