Influence of adrenomedullin on tone of isolated bovine retinal arteries

PURPOSE. To assess and characterize the vasorelaxing effect of adrenomedullin (AM) on isolated bovine retinal arteries (BRAS). METHODS. Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of AM (1 pM to 0.1 muM) to the organ bath. RESULTS. AM caused a concentration-dependent relaxation of the BRAS. Removal of the endothelium of the BRAS, inhibition of nitric oxide synthase with N-(omega) over bar-nitro-L-arginine (L-NA) or inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) significantly reduced the AM response. Cyclooxygenase inhibition with indomethacin or sodium diclofenac did not reduce, but rather increased, vasodilation. The AM-receptor antagonist AM 22-52 slightly, but significantly, reduced the AM response, whereas the CGRP-receptor antagonist CGRP 8-37 caused a more pronounced reduction. The adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (8-SPT) did not affect AM-induced vasorelaxation. Inhibition of several intracellular calcium ([Ca2+](i))-reducing mechanisms failed to block the relaxation induced by AM. Only inhibition of the plasma membrane Ca2+-adenosine triphosphatase (ATPase) with vanadate significantly attenuated the AM response. CONCLUSIONS. AM induces vasodilation in isolated bovine retinal arteries. Endothelium-derived NO and stimulation of CGRP- and AM-receptors appear to be involved in the AM response, whereas prostanoids and activation of adenosine receptors are not involved. Activation of Ca2+-extrusion by the plasma membrane Ca2+-ATPase may elicit the relaxation of BRAS in response to AM.