(761.15) Activation of Sympathetic Nervous System Contributes to Erthroprotein Gene Upregulation by Hypobaric Hypoxia

Poster Board Number: E518

Xiaoyu Su (Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, , Biological Sciences Division, University of Chicago), Timothy Matthews (Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, , Biological Sciences Division, University of Chicago), Matthew Hildreth (Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, , Biological Sciences Division, University of Chicago), Ying-Jie Peng (Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, , Biological Sciences Division, University of Chicago), Jayasri Nanduri (Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, , Biological Sciences Division, University of Chicago), Nanduri Prabhakar (Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, , Biological Sciences Division, University of Chicago)

Hypobaric hypoxia (HH) experienced at high altitude initiates a series of physiological adaptations to maintain homeostasis. One such adaptation is the activation of the Epo gene which encodes the glycoprotein hormone erythropoietin (EPO). Increased circulating EPO levels defend against HH by facilitating blood O2 transport through increasing red blood cell production. HH also increases blood pressure (BP) through activation of the sympathetic nervous system and the ensuing elevation of circulating catecholamine levels. The present study examined the role of sympathetic nerve activation in HH-evoked Epo gene activation and elevated circulating levels of EPO. Studies were performed on adult, male wild-type (WT) mice treated with 18 hours of HH (0.4 atmospheres), simulating low O2 condition experienced at high altitude. Our results showed increased renal Epo gene abundance and elevated plasma EPO levels. Remarkably, these responses were either markedly attenuated or absent in mice with selective ablation of adrenal medulla as well as after treatment with propranolol, a non-selective beta-adrenergic receptor blocker. Moreover, infusion of epinephrine alone activated renal Epo gene and elevated plasma EPO levels. These results suggest that sympathetic nerve activation and the ensuing increase in plasma epinephrine contribute to Epo gene activation by HH.

(Supported by NIH-HLBI P01-HL-44454)