thromboxane-a2--carbocyclic and 9-(tetrahydro-2-furyl)-adenine

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(-10) to 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 A(2). In contrast, selective A(2)-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 A(2) receptor-mediated OMDVR dilation.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adenine; Adenosine; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Angiotensin II; Animals; Calcimycin; Calcium; Colforsin; Cyclic AMP; Cyclooxygenase Inhibitors; Endothelium, Vascular; Enzyme Inhibitors; Female; Ionophores; Kidney Medulla; Kinetics; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; omega-N-Methylarginine; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1; Signal Transduction; Thromboxane A2; Vasodilation