PLASMA ERYTHROPOIETIN CONCENTRATION DETERMINE THE CAROTID BODY CHEMOSENSITIVITY TO HYPOXIA AND HYPERCAPNIA IN RATS

Abstract

We tested the hypothesis that Erythropoietin (Epo) have an impact in the modulation of carotid body (CB) chemoreceptors in response to hypoxia and hypercapnia. To study this subject, we used isolated and perfused ex vivo CB preparations from adult male Sprague Dawley rats. Prior evaluation of the carotid sinus nerve activity (CSNA ‐ throughout a suction glass electrode encircling and sealing the junction of the carotid body and the carotid sinus nerve), preparations were incubated for 1h with (or without) Epo at different concentrations. Then CBs were exposed to hypoxic and hypercapnic conditions. Normoxic baseline activity was not affected by any tested Epo concentration. However, under hypoxia and hypercapnia, Epo doses lower than 0.5U/ml increased the CSNA (by almost 40%), Epo doses higher than 0.5U/ml gradually decreased the CSNA in hypoxic and hypercapnic condition. Complete inhibition of CSNA was reached when preparations were incubated with 2U/ml of Epo concentration. Keeping in mind that nitric oxide (NO) in CB is an inhibitory messenger and that Epo in combination with low oxygen tension increase the endothelial capacity to produce NO, preparations were incubated at the same time with Epo (at the inhibitory concentration of 1 U/ml) and NO inhibitors, 400 μM L‐NAME (Nitric synthase inhibitor) or 100 μM 7NI (specific neuronal Nitric oxide synthase inhibitor). Our results showed that inhibition of NO (with L‐NAME and 7NI) fully restored the hypoxic CSNA. Similar results were found by exposing CB preparations to hypercapnic conditions. Accordingly, to these findings, immunohistochemistry studies showed a dense staining of Epo receptors (EpoR) in the carotid bodies, apparently localized within islets of chemosensitive cells. In summary, our results strongly suggest that the plasma Epo concentration determines the CB chemo‐response to hypoxic and hypercapnic conditions. These novel findings are relevant to better understand respiratory disorders, including those occurring at high altitude.Support or Funding InformationCIHR, Région Rhône Alpes and consulat de France in QuébecThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.