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Merck

Acute hemodynamic effects of erythropoietin do not mediate its cardioprotective properties.

Biology open (2012-12-06)
Ismayil Ahmet, Edward G Lakatta, Mark I Talan
ANOTACE

Activation of nitric oxide (NO) signaling is considered, at list partially, a mechanistic basis for EPO-induced cardioprotection. Surprisingly, hemodynamic response subsequent to NO activation after EPO administration has never been reported. The objectives of this study were to evaluate the acute hemodynamic and cardiovascular responses to EPO administration, to confirm their NO genesis, and to test the hypothesis that EPO-induced cardioprotection is mediated through cardiovascular changes related to NO activation. In Experiment 1, after 3000 U/kg of rhEPO was administered intravenously to Wistar rats, arterial blood pressure, monitored via indwelling catheter, progressively declined almost immediately until it leveled off 90 minutes after injection at 20% below control level. In Experiment 2 the 25% reduction of mean blood pressure, compared to control group, was observed 2 hours after intravenous injection of either 3000 or 150 U/kg of rhEPO. Detailed pressure-volume loop analyses of cardiac performance (Experiment 3) 2 hours after intravenous injection of human or rat recombinant EPO (3000 U/kg) revealed a significant reduction of systolic function (PRSW was 33% less than control). Reduction of arterial blood pressure and systolic cardiac function in response to rhEPO were blocked in rats pretreated with a non-selective inhibitor of nitric oxide synthase (L-NAME). In Experiment 4, 24 hours after a permanent ligation of a coronary artery, myocardial infarction (MI) measured 26±3.5% of left ventricle in untreated rats. MI in rats treated with 3000 U/kg of rhEPO immediately after coronary ligation was 56% smaller. Pretreatment with L-NAME did not attenuate the beneficial effect of rhEPO on MI size, while MI size in rats treated with L-NAME alone did not differ from control. Therefore, a single injection of rhEPO resulted in a significant, NO-mediated reduction of systemic blood pressure and corresponding reduction of cardiac systolic function. However, EPO-induced protection of myocardium from ischemic damage is not associated with NO activation or NO-mediated hemodynamic responses.

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Erythropoietin from rat, recombinant, expressed in insect cells, suitable for cell culture