Adenosine, Adenosine Receptors and Neurohumoral Syncope: From Molecular Basis to Personalized Treatment

Adenosine is a ubiquitous nucleoside that is implicated in the occurrence of clinical manifestations of neuro-humoral syncope (NHS). NHS is characterized by a drop in blood pressure due to vasodepression together with cardio inhibition. These manifestations are often preceded by prodromes such as headaches, abdominal pain, feeling of discomfort or sweating. There is evidence that adenosine is implicated in NHS. Adenosine acts via four subtypes of receptors, named A(1)(A(1)R), A(2)A (A(2A)R), A(2B) (A(2B)R) and A(3) (A3R) receptors, with all subtypes belonging to G protein membrane receptors. The main effects of adenosine on the cardiovascular system occurs via the modulation of potassium ion channels (IKAdo, K-ATP), voltage-gate calcium channels and via cAMP production inhibition (A(1)R and A(3)R) or, conversely, through the increased production of cAMP (A(2A/B)R) in target cells. However, it turns out that adenosine, via the activation of A(1)R, leads to bradycardia, sinus arrest or atrioventricular block, while the activation of A(2A)R leads to vasodilation; these same manifestations are found during episodes of syncope. The use of adenosine receptor antagonists, such as theophylline or caffeine, should be useful in the treatment of some forms of NHS. The aim of this review was to summarize the main data regarding the link between the adenosinergic system and NHS and the possible consequences on NHS treatment by means of adenosine receptor antagonists.

Automated summary

Adenosine plays a role in neuro-humoral syncope through its interaction with different receptor subtypes. The modulation of ion channels, calcium channels, and cAMP production are involved in adenosine's effects on the cardiovascular system. Adenosine receptor antagonists may be useful in the treatment of syncope.