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 ef fects of this hormone on the vasodilatation induced by either acetylch oline, which is endothelium-dependent, and nitroprusside, which is end othelium-independent. Experiments were carried out in 12 healthy volun teers. Graded doses of rHuEPO (25, 50, 500 U/min), acetylcholine (7.5 and 15 mu g/min), sodium nitroprusside (3 and 10 mu g/min), and saline solution (sodium chloride 0.9%) were infused in the dorsal pedal arte ry of the lower limb. rHuEPO reduced the cutaneous temperature in a do se-dependent manner compared to the saline solution, thus suggesting t hat the hormone causes vasoconstriction. In contrast graded doses of a cetylcholine and nitroprusside provoked vasodilatation: in fact both i ncreased the cutaneous temperature compared to controls in a dose depe ndent manner. The infusion of vasoconstrictive doses of rHuEPO in asso ciation with acetylcholine (15 mu g/min) reverted the increase in the cutaneous temperature induced by the endothelium-dependent vasodilator . In contrast rHuEPO administered in combination with nitroprusside fa iled to block the vasodilatation induced by the endothelium-independen t vasodilator. Therefore our data suggest that rHuEPO exerts an indire ct vasoconstrictive effect and that acetylcholine-induced vasodilatati on, which is endothelium-dependent, is blunted by the vasoconstrictive activity of rHuEPO, thus demonstrating that the hormone may impair th e synthesis of endothelial nitric oxide.