The effect of centrally administered erythropoietin on cardiovascular and respiratory system of anaesthetized rats

Abstract

Erythropoietin (EPO) is a hematopoietic factor, which is produced primarily by the adult kidney in response to tissue hypoxia. There is strong evidence that EPO may also be synthesized in the brain and act as a neuroprotector or neuromodulator in the central nervous system. The present study investigated the effect of centrally administered EPO on cardiovascular and respiratory parameters in anaesthetized rats. The animals were anaesthetized with ketamine (70 mg/kg) and xylazine (10 mg/kg) mixture. EPO at doses of 0.06, 0.12, 0.25 and 0.50 IU/5 mu l or 0.9% saline as a control were injected intracerebroventricularly and blood pressure, heart rate, respiratory rate, tidal volume and minute ventilation were recorded. Following the administration of EPO, there was a significant increase in blood pressure, heart and respiratory rates, tidal volume and minute ventilation which were time and dose dependant. In order to investigate whether these effects of centrally injected EPO was caused by the diffusion of the drug to the periphery, the highest dose EPO (0.5 IU) in the present study, was injected intravenously but intravenously injected EPO showed no significant effect in these parameters. In conclusion, our findings showed that centrally injected erythropoietin caused pressor and tachycardic response, an increase in respiratory frequency and volume in anaestlietized rats. Moreover intravenous injection of the highest dose of EPO used in the study caused no effect suggesting a central mechanism of action for the agent. Hence, one can hypothesize that erythropoietin may play a role in the central regulation of cardiovascular and respiratory system as a neuromodulator or neuromediator.