1) From discovery by Bergantin et al. (Cell Calcium, 2013) of involvement of interaction of intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP interaction) in the paradoxical sympathetic hyperactivity produced by L-type CCB during antihypertensive therapy (phenomenon entitled as “calcium paradox”); 2) Physiological and pathological role of Ca2+/cAMP interaction on the secretory response of sympathetic neurons and adrenal chromaffin cells; 3) Potential pharmacological therapeutic translation to human health and disease of the “calcium paradox”: hypertension, neurological/psychiatric disorders (Alzheimer´s and Parkinson´s diseases, and depression) and drug interaction in practical medicine.