Targeting adenosine receptors in the development of cardiovascular therapeutics

Adenosine receptor stimulation has negative inotropic and dromotropic actions, reduces cardiac ischemia-reperfusion injury and remodeling, and prevents cardiac arrhythmias. In the vasculature, adenosine modulates vascular tone, reduces infiltration of inflammatory cells and generation of foam cells, and may prevent the development of atherosclerosis as a result. Modulation of insulin sensitivity may further add to the anti-atherosclerotic properties of adenosine signaling. In the kidney, adenosine plays an important role in tubuloglomerular feedback and modulates tubular sodium reabsorption. The challenge is to take advantage of the beneficial actions of adenosine signaling while preventing its potential adverse effects, such as salt retention and sympathoexcitation. Drugs that interfere with adenosine formation and elimination or drugs that allosterically enhance specific adenosine receptors seem to be most promising to meet this challenge.