A Tantalizing Target for the Treatment of Salt-Sensitive Hypertension
See related article, pp 511–521
Adenosine is an important extracellular signaling molecule that regulates cellular responses to hypoxia, energy depletion, and tissue injury via activation of G-protein–coupled receptors.1,2 There are 4 adenosine receptor subtypes, A1 A2A, A2B, and A3; these are ubiquitously expressed on almost all cell types.2 Both under- and overactivation of adenosine receptors have been implicated in cardiovascular diseases, such as diabetes mellitus, heart failure, and hypertension.3 Thus, for several decades, adenosine receptors have appeared as a tantalizing target for the treatment of cardiovascular disease.
Despite significant research over the past 25 years seeking to understand the roles of adenosine receptors in the cardiovascular system, it has been difficult to unmask their therapeutic potential. This is likely because of the widespread expression of adenosine receptors and the fact that adenosine is a potent agonist at all subtypes.1,3 This has led to the realization that intervention may need to be directed against local paracrine adenosine systems, as global adenosine receptor targeting may not only block pathological processes but also prevent beneficial roles of adenosine.1 The lack of specific …