The Effects of Erythropoietin on the Respiratory Function: Measurements of Respiratory Mechanics in the Rat

Abstract

Data reported in the literature indicate that erythropoietin (EPO) influences mammals respiratory function, for example stimulating pulmonary ventilation. Direct experimentations about possible effects of EPO on respiratory mechanics are lacking. In the present report, the endinflation occlusion method was applied in control and EPO-treated anaesthetised and positive-pressure ventilated rats to assess respiratory mechanics. The method involves a sudden flow arrest after a constant flow inflation, and allows to measure the ohmic airway resistance and the respiratory system elastance. A significant decrement of the ohmic airway resistance after 20 and 30 minutes from i.p. EPO administration was observed in experimental animals, which was not seen in control animals. The elastic characteristics of the respiratory system did not change over time in both groups. Hypothesis about the mechanism(s) explaining the results and potential applications to humans are addressed. In particular, further data were obtained by performing additional experiments suggesting that the observed airway resistance decrement may be related to an EPO-induced increased nitric oxide production, a rather well known bronchodilator agent. Literature and present results indicate that the spontaneous increments of plasmatic EPO concentrations, such as those happening in hypoxia and/or blood loss, may be associated with airway resistance decrement. It is suggested that erythropoietin, beside the well known effect on haematopoiesis, may activate complex physiological responses including haematological, circulatory and respiratory adaptations to hypoxia in mammals. Keywords: Airway resistance, end-inflation occlusion method, erythropoietin, hypoxia, rat, respiratory mechanics.