Afferent arteriolar adenosine A(2a) receptors are coupled to K-ATP in in vitro perfused hydronephrotic rat kidney

Adenosine is known to exert dual actions on the afferent arteriole, eliciti ng vasoconstriction, by activating A(1) receptors, and vasodilation at high er concentrations, by activating lower-affinity A(2) receptors. We could de monstrate both of these known adenosine responses in the in vitro perfused hydronephrotic rat kidney. Thus, 1.0 mu M adenosine elicited a transient va soconstriction blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and 1 0-30 mu 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-affin ity adenosine vasodilatory response was observed at concentrations of 10-30 0 nM. This response was blocked by both 4-(2-[7-amino-2-(2-furyl)[1,2,4]tri azolo [2,3-a] [1,3,5] triazin-5-yl-amino] ethyl)phenol (ZM-241385) and glib enclamide and was mimicked by 2-phenylaminoadenosine (CV-1808) (IC50 Of 100 nM), implicating adenosine A(2a) receptors coupled to ATP-sensitive K chan nels (K-ATP) Like adenosine, 5'-N-ethylcarboxamidoadenosine (NECA) elicited both glibenclamide-sensitive and glibenclamide-insensitive vasodilatory re sponses. The order of potency for the glibenclamide-sensitive component was NECA > adenosine = CV-1808. Our findings suggest that, in addition to the previously described adenosine A(1) and low-affinity A(2b) receptors, the r enal microvasculature is also capable of expressing high-affinity adenosine A(2a) receptors. This renal adenosine receptor elicits afferent arteriolar vasodilation at submicromolar adenosine levels by activating K-ATP.