Acute, NO‐mediated, effects of erythropoietin are not associated with its cardioprotective properties

Abstract

Our serendipitous observation of acute reduction of blood pressure associated with a systemic injection of recombinant human erythropoietin (rhEPO) in the rat prompted a systematic evaluation of the acute effects of rhEPO on cardiovascular function and cardioprotection. Four groups of rats (Wistar, male, 3‐mo old) received bolus i.v. injection of one of the following: physiological saline, rhEPO (3000 U/kg), saline+L‐NAME (15 mg/kg), or rhEPO+L‐NAME. Two hours after injections rats were anesthetized with Isoflurane and subjected to detailed analyses of cardiovascular performance via open chest pressure‐volume loops analyses. In the second experiment four groups of rats were subjected to a permanent ligation of descending coronary artery immediately followed by the same i.v. injections as in the first experiment. Twenty four hours following coronary ligation hearts were harvested and myocardial infarct size (MI) was measured histologically. A significant reduction of arterial blood pressure two hours after a rhEPO injection was accompanied with a reduction of left ventricular systolic function (Table). L‐NAME completely suppressed this acute cardiovascular response to rhEPO. In contrast, the 50% reduction of MI size observed 24 hrs after coronary ligation in rhEPO‐treated vs untreated rats was not affected by L‐NAME treatment. Thus, these novel NO‐mediated acute hemodynamic effects of rhEPO are not associated with EPO‐associated cardioprotection. Parameters Saline rhEPO ESP 85±5 66±5* dP/dt+ 7136±530 5420±382* PRSW 51.8±3.9 34.6±2.5* BPs 90±6 70±3* BPd 55±5 38±3 BPm 66±6 49±3* ‐p<0.05