Adenosine A2 Receptor Activation Attenuates Afferent Arteriolar Autoregulation During Adenosine Receptor Saturation in Rats

Abstract

Adenosine is an important paracrine agent regulating renal hemodynamics via adenosine A1 and A2 receptors. To determine the interactions between adenosine A1 and A2 receptors and the possible role of adenosine as a modulator of afferent arteriolar autoregulatory responses, videomicroscopic measurements of afferent arteriolar dimensions were performed at different perfusion pressures (from 100 to 125 and 150 mm Hg) using the isolated-blood–perfused rat juxtamedullary nephron preparation. Single afferent arterioles were visualized and superfused with low or high concentrations of adenosine, either alone or with the adenosine A1 receptor antagonist 8-noradamantan-3-yl-1,3-dipropylxanthine (10 μmol/L) or the adenosine A2 receptor antagonist dimethyl-1-propargylxanthine (10 μmol/L). Adenosine (20 μmol/L) decreased afferent arteriolar diameter by −9.0±0.9%, and this effect was enhanced by dimethyl-1-propargylxanthine (10 μmol/L) to −16.1±1.2%. However, autoregulatory capability was maintained. Adenosine-induced vasoconstriction was prevented by 8-noradamantan-3-yl-1,3-dipropylxanthine (10 μmol/L) with diameter increasing by 9.6±1.2%. Adenosine receptor saturation with a high concentration of adenosine (120 μmol/L) or blocking A1 receptors with 8-noradamantan-3-yl-1,3-dipropylxanthine in the presence of adenosine resulted in marked vasodilation and marked impairment of autoregulatory responses to increases in perfusion pressure (−1.5±1.1% and −3.5±0.9%). However, afferent arteriolar autoregulatory responses to elevations in perfusion pressure were restored after blockade of A2 receptors alone or in combination with A1 receptor blockade. During treatment with dimethyl-1-propargylxanthine in the presence of adenosine receptor saturation (120 μmol/L), afferent arteriolar autoregulatory responses were intact (−16.5±1.6% and −26.4±2.1%). These results indicate that the interactions between adenosine A1 and A2 receptors exert important modulatory influences on afferent arteriolar tone and autoregulatory capability. Activation of A2 receptors abrogates the counteracting influences of A1 receptors leading to marked vasodilation and decreased afferent arteriolar autoregulatory efficiency.