Altered pulmonary vascular reactivity in mice with excessive erythrocytosis

Jo Hasegawa, Klaus F. Wagner, Dörte Karp, Dechun Li, Junpei Shibata, Matthias Heringlake, Ludger Bahlmann, Reinhard Depping, Joachim Fandrey, Peter Schmucker, Stefan Uhlig

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Pulmonary vascular remodeling during chronic hypoxia may be the result of either oxygen deprivation or erythrocytosis. To separate experimentally the effects of hypoxia and erythrocytosis, we analyzed transgenic mice that constitutively overexpress the human erythropoietin gene in an oxygen-independent manner. These mice are characterized by polycythemia but have normal blood pressure, heart rate, and cardiac output. In transgenic mice, pulmonary artery pressure (PAP) was increased in vivo but was reduced in blood-free perfused lungs. The thromboxane receptor agonist U46619 caused a smaller rise in PAP in isolated transgenic lungs than in lungs from wild-type mice. The transgenic pulmonary vasculature was characterized by elevated prostacyclin production, stronger endothelial nitric oxide synthase expression, and reduced pulmonary vascular smooth muscle thickness. The fact that transgenic polycythemic mice have marked pulmonary hypertension in vivo but not in vitro suggests that their pulmonary hypertension is due to the increased blood viscosity, thus supporting an independent role of polycythemia in the development of pulmonary hypertension. In addition, our findings indicate that the lungs of transgenic animals adapt to the high PAP by elevated synthesis of vasodilators and reduced vascular smooth muscle thickness that tend to reduce vascular tone and vascular responsiveness.

Original languageEnglish
Pages (from-to)829-835
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume169
Issue number7
DOIs
Publication statusPublished - 01-04-2004

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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