Afferent arteriolar adenosine [A.sub.2a] receptors are coupled to [K.sub.ATP] in in vitro perfused hydronephrotic rat kidney

Tang, Lilong, Michael Parker, Qing Fei, and Rodger Loutzenhiser. Afferent arteriolar adenosine [A.sub.2a] receptors are coupled to [K.sub.ATP] in in vitro perfused hydronephrotic rat kidney. Am. J. Physiol. 277 (Renal Physiol. 46): F926-F933, 1999.--Adenosine is known to exert dual actions on the afferent arteriole, eliciting vasoconstriction, by activating A1 receptors, and vasodilation at higher concentrations, by activating lower-affinity [A.sub.2] receptors. We could demonstrate both of these known adenosine responses in the in vitro perfused hydronephrotic rat kidney. Thus, 1.0 [micro]M adenosine elicited a transient vasoconstriction blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and 10-30 [micro]M adenosine reversed KCl-induced vasoconstriction. However, when we examined the effects of adenosine on pressure-induced afferent arteriolar vasoconstriction, we observed a third action. In this setting, a high-affinity adenosine vasodilatory response was observed at concentrations of 10-300 [micro]M. This response was blocked by both 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a] [1,3,5]triazin-5-yl-amino]ethyl)phenol (ZM-241385) and glibenclamide and was mimicked by 2-phenylaminoadenosine (CV-1808) ([IC.sub.50] of 100 nM), implicating adenosine [A.sub.2a] receptors coupled to ATP-sensitive K channels ([K.sub.ATP]). Like adenosine, 5'-N-ethylcarboxamidoadenosine (NECA) elicited both glibenclamide-sensitive and glibenclamide-insensitive vasodilatory responses. The order of potency for the glibenclamidesensitive component was NECA [is greater than] adenosine = CV-1808. Our findings suggest that, in addition to the previously described adenosine [A.sub.1] and low-affinity [A.sub.2b] receptors, the renal microvasculature is also capable of expressing high-affinity adenosine [A.sub.2a] receptors. This renal adenosine receptor elicits afferent arteriolar vasodilation at submicromolar adenosine levels by activating [K.sub.ATP]. ATP-sensitive potassium channels; glibenclamide; CV-1808; 5'-N-ethylcarboxamidoadenosine; ZM-241385; renal microcirculation; afferent arteriole; hydronephrosis; myogenic vasoconstriction; adenosine 3',5'-cyclic monophosphate; Ro-20-1724