Relationship between erythropoietin and nitric oxide in the contraction ofrat renal arcuate arteries and human umbilical vein endothelial cells

We have investigated the effects of recombinant human erythropoietin (EPO) on the responses of rat renal arcuate arteries to dopamine, noradrenaline a nd acetylcholine and on the release of NO from human umbilical vein endothe lial cells (HUVEC) in culture. Noradrenaline induced a concentration-depend ent constriction and acetylcholine a concentration-dependent relaxation of the vessels. The effects of dopamine were concentration-dependent, leading to relaxation of the vessels at low concentrations and contraction of the v essels at high concentrations. N-G-Nitro-L-arginine methyl ester (L-NAME; 0 .1 mM) did not change the vasoconstrictor responses to noradrenaline and do pamine, but inhibited the acetylcholine- and dopamine-induced vasorelaxatio n. Neither 0.1 nor 20 units . ml(-1) EPO affected noradrenaline-induced con striction, or dopamine- or acetylcholine-induced relaxation, of the vessels . EPO at 20 units . ml(-1) attenuated dopamine-induced constriction of the vessels. Th is effect was blunted by application of L-NAME, suggesting that EPO may stimulate dopamine-mediated NO release from these vessels. EPO sti mulated NO release from the resting HUVEC in a concentration- and time-depe ndent manner, an effect that was inhibited by the presence of N-G-nitro-L-a rginine, These data suggest that, in vitro, EPO is able to stimulate NO rel ease from rat renal arcuate arteries and HUVEC in culture. Whether these ac ute short-term actions can be related to the longer-term actions of EPO rem ains to be resolved.