ERYTHROPOIETIN MODIFIED THE CARDIAC ACTION OF OUABAIN IN CHRONICALLY ANEMIC-UREMIC RATS

The results of the studies reported here demonstrate the cardiac non-h aematopoietic effect of erythropoietin, providing a new physiological function of the hormone. We demonstrate that myocardium from rat with chronic renal failure (CRF) showed an abnormal reponse to ouabain asso ciated with an inhibition of cardiac Na+/K+/ATPase activity and with a decrease in the high affinity H-3-ouabain binding sites. The extent t o which both actions were improved with the recombinant human erythrop oietin (rHuEpo) treatment suggests that the lack of the hormone is res ponsible for this phenomenon. The fact is that neither contractile nor enzymatic action of rHuEpo was accompanied with the improvement of th e functional renal and haematologic parameters, indicating a primary e ffect on myocardial contractile function of rHuEpo, independent of the anaemic and uraemic state of the animal. The reason why erythropoieti n is able to modulate directly the cardiac Na+/K+ pump makes it possib le to conclude that the lack of erythropoietin in CRF may be at least in part responsible for the inhibition of cardiac enzymes, altering th e contractile behaviour of the heart.