Recombinant human erythropoietin inhibits the cutaneous vasodilatation induced by acetylcholine

We investigated by means of telethermography the contractile response of cutaneous vessels to recombinant erythropoietin (rHuEPO) and the effects of this hormone on the vasodilatation induced by either acetylcholine, which is endothelium-dependent, and nitroprusside, which is endothelium-independent. Experiments were carried out in 12 healthy volunteers. Graded doses of rHuEPO (25, 50, 500 U/min), acetylcholine (7.5 and 15 micrograms/min), sodium nitroprusside (3 and 10 micrograms/min), and saline solution (sodium chloride 0.9%) were infused in the dorsal pedal artery of the lower limb. rHuEPO reduced the cutaneous temperature in a dose-dependent manner compared to the saline solution, thus suggesting that the hormone causes vasoconstriction. In contrast graded doses of acetylcholine and nitroprusside provoked vasodilatation: in fact both increased the cutaneous temperature compared to controls in a dose-dependent manner. The infusion of vasoconstrictive doses of rHuEPO in association with acetylcholine (15 micrograms/min) reverted the increase in the cutaneous temperature induced by the endothelium-dependent vasodilator. In contrast rHuEPO administered in combination with nitroprusside failed to block the vasodilatation induced by the endothelium-independent vasodilator. Therefore our data suggest that rHuEPO exerts an indirect vasoconstrictive effect and that acetylcholine-induced vasodilatation, which is endothelium-dependent, is blunted by the vasoconstrictive activity of rHuEPO, thus demonstrating that the hormone may impair the synthesis of endothelial nitric oxide.