Role of erythropoietin and nitric oxide in modulating the tone of human renal interlobular and subcutaneous arteries from uraemic subjects

This study investigated potential reasons why erythropoietin (EPO) given th erapeutically to patients with renal failure may increase peripheral, but n ot renal, vascular resistance. This was done by comparing the effects of EP O on resting tension in normal renal interlobular and subcutaneous vessels from uraemic patients. In human subcutaneous arteries from uraemic subjects , noradrenaline- and KCl-induced vasoconstrictions were enhanced when nitri c oxide (NO) production was blocked with N-G-nitro-L-arginine methyl ester (L-NAME), but were unaffected by EPO, while acetylcholine- and bradykinin-i nduced concentration-dependent relaxations were markedly attenuated by L-NA ME, but not by EPO. The noradrenaline- and KCl-induced vasoconstrictions of human renal interlobular arteries were unaffected by the presence of L-NAM E, but were attenuated by EPO (20 units.ml(-1)) by some 33% (P < 0.01); thi s effect was enhanced by the co-ad ministration of L-NAME. Acetylcholine an d bradykinin caused comparable dilatations of the interlobular arteries; th e response to the former was attenuated by L-NAME, but none of these respon ses were changed by EPO. EPO given alone, at a concentration of either 0.1 or 20 units.ml(-1), had no effect on basal resting tone. NO production medi ated both acetylcholine- and bradykinin-induced relaxation in this vessel t ype. In contrast, in the interlobular arteries there was no indication of N O modulating the level of vasoconstriction, and it only mediated acetylchol ine-induced dilation. These acute responses to EPO only partially explain i ts differential effects on the vasculature in renal failure.