Adenosine signaling in outer medullary descending vasa recta

Abstract

We tested whether dilation of outer medullary descending vasa recta (OMDVR) is mediated by cAMP, nitric oxide (NO), and cyclooxygenase (COX). Adenosine (A; 10−6 M)-induced vasodilation of ANG II (10−9 M)-preconstricted OMDVR was mimicked by the cAMP analog 8-bromoadenosine 3′,5′-cyclic monophosphate (10−10to 10−4 M) and reversed by the adenylate cyclase inhibitor SQ-22536. Adenosine (10−4 M) stimulated OMDVR cAMP production greater than threefold. NO synthase blockade with N G-nitro-l-arginine methyl ester and N G-monomethyl-l-arginine (10−4 M) did not affect adenosine vasodilation. Adenosine induced endothelial cytoplasmic calcium transients that were small. Indomethacin (10−6 M) reversed adenonsine-induced dilation of OMDVR preconstricted with ANG II, endothelin, 4-bromo-calcium ionophore A23187, or carbocyclic thromboxane A2. In contrast, selective A2-receptor activation dilated endothelin-preconstricted OMDVR even in the presence of indomethacin. We conclude that OMDVR vasodilation by adenosine involves cAMP and COX but not NO. COX blockade does not fully inhibit selective A2 receptor-mediated OMDVR dilation.