Afferent arteriolar vasodilator effect of adenosine predominantly involves adenosine [A.sub.2B] receptor activation

Adenosine is an important paracrine agent regulating renal vascular tone via adenosine [A.sup.1] and [A.sup.2] receptors. While A2B receptor message and protein have been localized to preglomerular vessels, functional evidence on the role of [A.sup.2]B receptors in mediating the vasodilator action of adenosine on afferent arterioles is not available. The present study determined the role of [A.sup.2]B receptors in mediating the afferent arteriolar dilation and compared the effects of [A.sup.2]B and [A.sup.2]A receptor blockade on afferent arterioles. We used the rat in vitro blood-perfused juxtamedullary nephron technique combined with videomicroscopy. Single afferent arterioles of Sprague-Dawley rats were visualized and superfused with solutions containing adenosine or adenosine [A.sup.2] receptor agonist (CV-1808) along with adenosine [A.sup.2]B and [A.sup.2]A receptor blockers. Adenosine (10 [micro]mol/1) caused modest constriction and subsequent superfusion with SCH-58261 (SCH), an [A.sup.2A] receptor blocker, at concentrations up 10 [micro]mol/1 elicited only slight additional decreases in afferent arteriolar diameter with maximum effect at a concentration of 1 [micro]mol/l (- 11.0 [+ or -] 2.5%, n = 6, P < 0.05). However, superfusion of adenosine-treated vessels with MRS-1754 (MRS), an [A.sup.2]B receptor blocker, elicited greater decreases in afferent arteriolar diameter (-26.0 [+ or -] 4.7%, n = 5, P < 0.01). SCH did not significantly augment the adenosine-mediated afferent constriction elicited by MRS; however, adding MRS after SCH caused further significant vasoconstriction. Superfusion with CV-1808 dilated afferent arterioles (17.2 [+ or -] 2.4%, n = 6, P < 0.01). This effect was markedly attenuated by MRS (-22.6 [+ or -] 2.0%, n = 5, P < 0.01) but only slightly reduced by SCH (-9.0 [+ or -] 1.1%, n = 5, P < 0.05) and completely prevented by adding MRS after SCH (-24.7 [+ or -] 1.8%, n = 5, P < 0.01). These results indicate that, while both [A.sup.2A] and [A.sup.2B] receptors are functionally expressed in juxtamedullary afferent arterioles, the powerful vasodilating action of adenosine predominantly involves [A.sup.2B] receptor activation, which counteracts [A.sup.1] receptor-mediated vasoconstriction. adenosine receptor antagonists; renal microcirculation; vascular biology; afferent arterioles; kidney doi: 10.1152/ajprenal.00149.2010.