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(Hypertension. 2007;50:744.)
© 2007 American Heart Association, Inc.

XVIIth Scientific Meeting of the Inter-American Society of Hypertension

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

From the Department of Physiology, Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, La.

Correspondence to Ming-Guo Feng, Department of Physiology, SL39, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112. E-mail mfeng{at}tulane.edu

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.

Key Words: renal autoregulation • microcirculation • adenosine receptors • tubuloglomerular feedback • ATP • kidney