Interactions of adenosine A1 and A2a receptors on renal microvascular reactivity

Adenosine vasoconstricts preglomerular arterioles via adenosine A1 receptors. Because adenosine also activates adenosine A2 receptors, its overall renal vascular actions are complex and not fully understood. The present study was performed to determine the relative contributions of adenosine A1 and A2a receptors to the responsiveness of the renal microvasculature to adenosine. Afferent and efferent arteriolar diameters were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. Basal afferent and efferent arteriolar diameters averaged 17.1 +/- 0.5 (n = 35) and 17.8 +/- 0.5 (n = 20) microm, respectively. Superfusion with 0.1 and 1 micromol/l adenosine did not significantly alter afferent and efferent arteriolar diameters; however, 10 micromol/l adenosine significantly reduced afferent and efferent arteriolar diameters (-8.2 +/- 0.8 and -5.7 +/- 0.6%, respectively). The afferent and efferent arteriolar vasoconstrictor responses to adenosine waned at a dose of 100 micromol/l, such that diameters returned to values not significantly different from control within 2 min. During adenosine A1 receptor blockade with 8-noradamantan-3-yl-1,3-dipropylxanthine (KW-3902: 10 micromol/l), 10 and 100 micromol/l adenosine significantly increased afferent diameter by, respectively, 8.1 +/- 1.2 and 13.7 +/- 1.3% (n = 14) and efferent arteriolar diameter by 6.4 +/- 1.3 and 9.3 +/- 1.2% (n = 8). The afferent and efferent arteriolar vasodilatory responses to adenosine in the presence of KW-3902 were significantly attenuated by addition of the adenosine A2a receptor antagonist 1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF-17837: 15 micromol/l, n = 7 and 6, respectively). The addition of KF-17837 alone significantly enhanced afferent (n = 15) and efferent (n = 6) arteriolar vasoconstrictor responses to 1, 10, and 100 micromol/l adenosine. These results indicate the presence of adenosine A1 and A2a receptors on afferent and efferent arterioles of juxtamedullary nephrons, such that adenosine A2a receptor-mediated vasodilation partially buffers adenosine-induced vasoconstriction in both pre- and postglomerular segments of the renal microvasculature.