Brief Review Role of Adenosine 5-Triphosphate in Regulating Renal Microvascular Function and in Hypertension

Abstract—ATP is an essential energy substrate for cellular metabolism, but it can also influence many biological processes when released into the extracellular milieu. Research has established that extracellular ATP acts as an autocrine/ paracrine factor that regulates many physiological functions. Alternatively, excessive extracellular ATP levels contribute to pathophysiological processes, such as inflammation, cell proliferation and apoptosis, and atherosclerosis. Renal P2 receptors are widely distributed throughout glomeruli, vasculature, and tubular segments and participate in controlling renal vascular resistance, mediating renal autoregulation, and regulating tubular transport function. This review will focus on the role of ATP-P2 receptor signaling in regulating renal microvascular function and autoregulation, recent advances on the role of ATP-P2 signaling in hypertension-associated renal vascular injury, and emerging new directions. (Hypertension. 2011;58:333-340.) Since ATP’s discovery as a coneurotransmitter nearly 40years ago,1 ATP is no longer regarded as just an intra-cellular energy source. Extracellular ATP is an autocrine/ paracrine factor that regulates many physiological functions, including neuronal signaling, control of vascular tone and reactivity, mechanosensation, and ion transport. Alterna-tively, excessive extracellular ATP levels contribute to patho-physiological processes, such as inflammation, cell prolifer-ation and apoptosis, and atherosclerosis.2 Extracellular ATP exerts its effects by activating distinct P2 purinoceptors, P2X and P2Y (Figure 1). P2X receptors are ligand-gated ion channels and exist as homotrimers (P2X1 to P2X7), meaning that 3 of the same subunit type associate to form a functional channel. They can also associate as multimeric complexes involving different types of P2X receptor subunits to for