Polycythemic responses to hypoxia: molecular and genetic mechanisms of chronic mountain sickness

responses to hypoxia: molecular and genetic mechanisms of chronic mountain sickness. J. Appl. Physiol. 84(4): 1242– 1251, 1998.—We examined erythropoietin (EPO) gene expres-sion and EPO production during hypoxia in two Sprague-Dawley rat strains with divergent polycythemic responses to hypoxia. Hilltop (H) rats develop severe polycythemia, severe hypoxemia, and pulmonary artery hypertension. The H rats often die from a syndrome indistinguishable from chronic mountain sickness (CMS) in humans. Madison (M) rats develop polycythemia and pulmonary artery hypertension that is modest and suffer no excess mortality. We tested the hypothesis that these rat strains have different stimulus-response characteristics governing EPO production. Rats of each strain were exposed to hypoxia (0.5 atm, 73 Torr inspired PO2), and renal tissue EPO mRNA and EPO levels, plasm