Erythropoietin dilates cerebral vessels

Abstract

Pharmacological doses of recombinant human erythropoietin (rhEPO) are neuroprotective when given to animals and humans after ischemic and traumatic brain injuries. Regulation of blood flow by dilation of cerebral arteries may be one mechanism by which rhEPO is neuroprotective. In the present study, we first sought to determine if the erythropoietin receptor (EPO-R) is present in resistance-sized cerebral arteries. Secondly, we tested the hypothesis that rhEPO directly interacts with cerebral vessels to alter vessel diameter. Immunohistochemistry for EPO-R on rat brain and middle cerebral artery (MCA) sections revealed that EPO-R is present on both vascular smooth muscle (VSM) and endothelial cells (ECs). Additionally, EPO-R was found in pial vessels and penetrating arterioles. To determine the effects of rhEPO on cerebrovascular tone, MCAs were isolated, mounted on glass micropipettes, and pressurized in a vessel chamber. Selective extraluminal application of rhEPO (0.001 – 10 U/mL) to the VSM of MCAs did not alter vessel diameter. Application of rhEPO to the lumen of MCAs, which preferentially targets the endothelium, resulted in concentration-dependent dilations (69.1% of maximal dilation in responding vessels with 10 U/mL rhEPO, p < 0.0001). In conclusion, EPO-Rs are located on both the endothelium and VSM of rat MCAs, and endothelial application of rhEPO dilates the MCA, likely by stimulating endothelial EPO-Rs. The neuroprotective effects of rhEPO may be mediated, in part, by the activation of EPO-R on cerebrovascular endothelial cells in resistance-sized arteries. T32 HL07939-01A2, F32 HL080916-01, RO1 NS38660 and AHA 027011N. T32 HL07939-01A2, F32 HL080916-01, RO1 NS38660 and AHA 027011N.