Relationship between erythropoietin and nitric oxide in the contraction of rat 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 and acetylcholine and on the release of NO from human umbilical vein endothelial cells (HUVEC) in culture. Noradrenaline induced a concentration-dependent 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 vessels at high concentrations. N(G)-Nitro-L-arginine methyl ester (L-NAME; 0.1 mM) did not change the vasoconstrictor responses to noradrenaline and dopamine, but inhibited the acetylcholine- and dopamine-induced vasorelaxation. Neither 0.1 nor 20 units.ml(-1) EPO affected noradrenaline-induced constriction, or dopamine- or acetylcholine-induced relaxation, of the vessels. EPO at 20 units. ml(-1) attenuated dopamine-induced constriction of the vessels. This effect was blunted by application of L-NAME, suggesting that EPO may stimulate dopamine-mediated NO release from these vessels. EPO stimulated NO release from the resting HUVEC in a concentration- and time-dependent manner, an effect that was inhibited by the presence of N(G)-nitro-L-arginine. These data suggest that, in vitro, EPO is able to stimulate NO release from rat renal arcuate arteries and HUVEC in culture. Whether these acute short-term actions can be related to the longer-term actions of EPO remains to be resolved.
Wu
X C
XC
Department of Physiology, Division of Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Johns
E J
EJ
Richards
N T
NT
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division; D046508:Culture Techniques; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine